Türk Üroloji Dergisi/Turkish Journal of Urology, 2018
Objective: This study was designed to evaluate the prevalence of Human Papilloma Virus (HPV) in s... more Objective: This study was designed to evaluate the prevalence of Human Papilloma Virus (HPV) in semen and document the cycle outcomes in couples with previous intra-cytoplasmic sperm injection (ICSI) failures. Material and methods: One hundred and seventeen couples with at least two ICSI attempts were included in the study. HPV infection in semen and DNA fragmentation in samples were analyzed by commercially available kits. The percentage of spermatozoa with fragmented DNA (DNA fragmentation index: DFI) was determined during fluorescence microscopic examination as previously described. The cycle outcomes of couples with or without HPV infected male partners were recorded. Results: According to our results, the prevalence of HPV was 7.7% in asymptomatic males with at least two previous ICSI failures. The increased DFI (>30%) was observed in 82.9% of the cases. In HPV-positive cases significantly lower number of good quality embryos were obtained. The implantation and pregnancy rates were similar in infected and non-infected males (p>0.05). The early miscarriage rate was slightly higher in HPV-positive group (33% vs. 10%, p>0.05). Conclusion: In cases with previous ICSI failures, the prevalence of HPV infection in semen is not higher than previously reported infertile populations. The reproductive outcome might be impaired in HPV-positive semen due to lower number of good quality embryos, which needs to be clarified by further large population-based studies.
Next-generation sequencing (NGS) technology is used to evaluate hereditary cancer risks of patien... more Next-generation sequencing (NGS) technology is used to evaluate hereditary cancer risks of patients worldwide; however, information concerning the germline multigene mutational spectrum among patients with breast cancer (BC) with consanguineous marriage (CM) is limited. Therefore, this prospective study aimed to determine the molecular characteristics of patients with BC who were tested with multigene hereditary cancer predisposition NGS panel and to show the effect of CM on cancer-related genes. Patients with BC with or without CM and family history (FH) of BC treated in our breast center were selected according to The National Comprehensive Cancer Network (NCCN) criteria for hereditary BC. In these patients, the analysis of a panel of 33 genes involved in hereditary cancer predisposition was performed after genetic counseling by using NGS. The pathogenic variant (PV) and the variant of uncertain significance (VUS) were found to be 15.8 and 47.4%, respectively. PVs were identified in 10/33 genes in 34 patients; 38.2% in BRCA1/2 genes; 6, 24, and 14% in other high, moderate and low-risk genes, respectively. The CM rate was 17.7% among the 215 patients with BC. The PV rate was 13.2% in patients with CM and 16.4% in patients without CM (P=0.80). When PV and VUS were evaluated together, the PV+VUS ratio was significantly higher in patients with CM and FH of BC than patients without CM and FH of BC (88.2 vs. 63.3%, P=0.045). Analysis of multigene panel provided 9.76% additional PVs in moderate/low-risk genes. The PV rate was similar in patients with BC with or without CM. A high PV+VUS ratio in patients with CM and FH of BC suggests that genes whose importance are unknown are likely to be pathogenic genes later.
Ajlan Tukun, MD, PhD, Prof. Medical Genetics. Current Institution: Duzen Laboratories, Ankara, aj... more Ajlan Tukun, MD, PhD, Prof. Medical Genetics. Current Institution: Duzen Laboratories, Ankara, [email protected] (orcid.org/0000-00017445-0918) Abstract Purpose: Infertility is one of the most common health problems affecting about one of five couples, and male factor contributes to a considerable proportion of this condition. This study aimed to detect DNA copy number variations of azoospermic males by high resolution comparative genomic hybridization and suggest candidate chromosomal loci associated with male infertility. Materials and methods: By using Comparative Genomic Hybridization (CGH), we aimed to detect previously unidentified genetic etiologic factors among infertile males. Thus it may be possible to explain some idiopathic cases and provide more accurate counselling to the affected couples. This technique may also allow predicting de novo infertility related loci. Results: A total of 90 patients were analyzed by comparative genomic hybridization. 49 patients revealed...
Cancer biomarkers : section A of Disease markers, 2021
BACKGROUND Due to the heterogeneous nature of Diffuse Large B-cell Lymphoma (DLBCL), the mechanis... more BACKGROUND Due to the heterogeneous nature of Diffuse Large B-cell Lymphoma (DLBCL), the mechanisms underlying tumor development and progression have not yet been fully elucidated. OBJECTIVE This study aimed to compare the characteristics of plasma exosomes of DLBCL patients and healthy individuals and to evaluate the exosomal interactions between DLBCL cell lines and normal B-cells. METHODS Exosome isolation was performed using an ultracentrifugation-based protocol from plasma of 20 patients with DLBCL and 20 controls. The expression of miRNAs from exosome samples was analyzed using a miRNA expression microarray. The presence of exosome-mediated communication between the lymphoma cells and normal B-cells was determined by the co-culture model. RESULTS A significant increase in plasma exosome concentrations of DLBCL patients was observed. There was also a significant decrease in the expression of 33 miRNAs in plasma exosomes of DLBCL patients. It was determined that normal B-cells i...
In this research, a simple method was used to synthesize poly(aniline-co-m-aminobenzoic acid) als... more In this research, a simple method was used to synthesize poly(aniline-co-m-aminobenzoic acid) also known as P(ANI-co-m-ABA) composite polystyrene (PS) nanofibers by using in situ chemical polymerization technique. The copolymer was polymerized on electrospun PS nanofibers mats with varied monomers solution concentration and the polymerization time. P(ANI-co-m-ABA) was also polymerized on PS films were prepared for comparison. The conductivity of the composites was studied and the result showed addition of graphene (GP) into the composites improved the conductivity of the composites. The composites of P(ANI-co-m-ABA)/PS nanofibers and films were characterized by Fourier transform infra-red (FTIR), thermogravimetric analysis (TGA) and ultraviolet visible (UV-vis) spectroscopy. Surface morphology of the composite was studied by scanning electron microscopy (SEM).
Journal of Pediatric Endocrinology and Metabolism, 2021
Objectives Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant condition cau... more Objectives Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant condition caused by heterozygous gain-of-function mutations in the human ALB gene. Case presentation We report, a three-year-old boy with FDH due to p.R242P (or p.R218P without signal peptide) mutation in the ALB gene with a phenotype characterized by extremely high serum total and free thyroxine concentrations. His parents had normal thyroid function tests (TFT), so the mutation detected in this patient is assumed “de novo”. Although the most frequent variant was p.R242H in Caucasians and p.R242P in Japanese, our patient had p.R242P variant. Conclusions Early identification of FDH is fundamental to prevent unnecessary repeats of TFT with different methods. We encourage the ALB gene hot spot sequencing initially and indicate that this molecular diagnosis is a rapid and simple method to diagnose FDH in individuals with euthyroid hyperthyroxinemia.
Pituitary-specific paired-like homeodomain transcription factor, PROP1, is associated with multip... more Pituitary-specific paired-like homeodomain transcription factor, PROP1, is associated with multiple pituitary hormone deficiency. Alteration of the gene encoding the PROP1 may affect somatotropes, thyrotropes, and lactotropes, as well as gonadotropes and corticotropes. We performed genetic analysis of PROP1 gene in a Turkish pedigree with three siblings who presented with short stature. Parents were first degree cousins. Index case, a boy, had somatotrope, gonadotrope, thyrotrope, and corticotrope deficiency. However, two elder sisters had somatotroph, gonadotroph, and thyrotroph deficiency and no corticotroph deficiency. On pituitary magnetic resonance, partial empty sella was detected with normal bright spot in all siblings. In genetic analysis, we found a gross deletion involving PROP1 coding region. In conclusion, we report three Turkish siblings with a gross deletion in PROP1 gene. Interestingly, although little boy with combined pituitary hormone deficiency has adrenocorticotr...
Recombinant chromosome 4 is a very rare chromosomal aberration with eighteen cases reported in th... more Recombinant chromosome 4 is a very rare chromosomal aberration with eighteen cases reported in the literature up to date. Here we report a five years old male patient with de novo rec(4) dup(4p) del(4q). The physical examination findings were as follows: caput quadratum, flat occiput, low frontal hairline, hypertelorism, ptosis, blepharophimosis, high arched eyebrows, flat nasal root with anteverted nostrils and short nose, long and smooth philtrum, thin upper lip with triangular mouth, microretrognathia, high arched palate, dental anomalies, large low-set ears, short neck, broad chest with widely spaced nipples, micropenis, cryptorchidism. Conventional cytogenetic analysis revealed the karyotype as 46,XY,rec(4)dup(4p14p16.3)del(4q34.3q35). Flourescence insitu hybridization (FISH) analysis with sub-telomeric probes for 4p and 4q showed duplication of 4p and deletion of 4q in recombinant chromosome 4. His parents' chromosomal analysis and sub-telomeric FISH analysis were both normal. The patient's final karyotype was reported as 46,XY,rec(4)dup(4p16.3p14)del(4q34.4q35).arr[h g19]4p16.3p14(68,345-36,018)x3,4q34.3q35(177,676,319-190,957,460)x1 detected by Microarray. According the literature all cases with recombinant chromosome 4 have similar clinical findings. Except for our case only one case in the literature has been reported to be de novo. In conclusion, we reported a very rare case of recombinant chromosome 4, which has the largest deletion and duplication in the literature. Further cases with similar findings would help the delineation of the findings associated with this chromosomal abnormality.
Amac: Infertilite, bes ciftten birini etkileyen, en yaygin saglik sorunlarindan biridir. Erkek fa... more Amac: Infertilite, bes ciftten birini etkileyen, en yaygin saglik sorunlarindan biridir. Erkek faktoru, bu durumun onemli bir kismini olusturur. Bu calismanin amaci, azoospermik erkeklerde karsilastirmali genomik hibridizasyon yontemi ile DNA kopya sayisi varyasyonlarinin ve aday kromozomal lokuslarin belirlenmesidir. Gerec ve Yontem: Bu calismada karsilastirmali Genomik Hibridizasyon (CGH) yontemiyle infertil erkeklerde daha once tanimlanamayan genetik etiyolojik faktorleri saptamayi amacladik. Dolayisiyla bazi idiyopatik vakalari aciklamak ve etkilenen ciftlere daha dogru danismanlik saglamak mumkun olabilir. Bu teknik ayni zamanda de novo infertiliteye iliskin lokuslerin tahmin edilmesine izin verebilecektir. Bulgular: Toplam 90 hasta karsilastirmali genomik hibridizasyon ile analiz edildi. 49 hasta en az bir bulgu ortaya cikarirken, 41 hastada (% 46) teknigimizle saptanan kopya sayisi degisimi yoktu. CNV lokuslarinda toplam 21 spermatogenez ile ilgili gen mevcuttu. Sonuc: Calismadan elde edilen veriler, infertil erkeklerin geleneksel yontemlerle saptanamayacak bazi DNA kopya sayisi varyasyonlari gosterebildiklerini gostermektedir. Ek verilerle, bu varyasyonlarin etyolojik onemini saptamak mumkun olabilir.
Presentación de casos clínicos RESUMEN El síndrome tricorrinofalángico (STRF) tipo II (sinónimo: ... more Presentación de casos clínicos RESUMEN El síndrome tricorrinofalángico (STRF) tipo II (sinónimo: síndrome de Langer-Giedion) es un síndrome autosómico dominante raro que afecta genes adyacentes y que se produce como resultado de una microdeleción que abarca los genes EXT1 y TRPS1 en la banda 8q24 (OMIM 150230). En este síndrome se combinan características de dos trastornos autosómicos dominantes: el síndrome tricorrinofalángico tipo I (OMIM 190350) y la osteocondromatosis múltiple hereditaria tipo I (OMIM 133700). El STRF tipo II se caracteriza por escaso cabello, nariz prominente y de extremo bulboso, surco nasolabial plano y alargado, epífisis de las falanges en forma de cono, retraso de la edad ósea durante la infancia y osteocondromas cartilaginosos múltiples. En este artículo presentamos el caso de un paciente de Turquía con las características clínicas y los signos óseos del STRF tipo II en el que se detectó una deleción de 13,8 Mb en las bandas 8q23.1-8q24.13. Palabras clave: síndrome tricorrinofalángico tipo II, deleción cromosómica, baja estatura.
Background: Glutaric aciduria type 1 (GA1) is a rare autosomal recessive neurometabolic disorder ... more Background: Glutaric aciduria type 1 (GA1) is a rare autosomal recessive neurometabolic disorder caused by mutations in the glutaryl CoA dehydrogenase gene (GCDH). If left untreated, it leads to accumulation of neurotoxic metabolites leading to poor neurological outcomes characterized by encephalopathic crises, subdural effusions and extrapyramidal features. Case presentation: We hereby report a consanguineous Sudanese family in which the father and two children were affected whilst the mother was an asymptomatic carrier. All had a novel guanine insertion in position c.1173_1174 (c.1173dupG), resulting in a frame shift and a stop codon downstream (p.Asn392Glufs4X). Conclusion: To our knowledge, this GCDH variant has not been previously reported. Genetic testing should be made widely available in communities where consanguinity is prevalent. This will allow detection of new pathogenic gene variants.
Trichorhinophalangeal syndrome type II (TRPSII) (synonym: Langer-Giedon syndrome) is a rare autos... more Trichorhinophalangeal syndrome type II (TRPSII) (synonym: Langer-Giedon syndrome) is a rare autosomal dominant contiguous gene syndrome, resulting from a microdeletion encompassing the EXT1 and the TRPS1 gene at 8q24 (MIM#150230). This syndrome combines the clinical features of two autosomal dominant disorders, trichorhinophalangeal syndrome type I (MIM#190350) and hereditary multiple osteochondromas type I (MIM # 133700). TRPSII is characterized by sparse scalp hair, a long nose with a bulbous tip, long flat philtrum, cone-shaped epiphyses of the phalanges, retarded bone age in infancy and multiple cartilaginous osteochondromas. We report a Turkish patient who had the clinical features and skeletal signs of TRPSII in whom a 13.8Mb deletion in 8q23.1- 8q24.13 was detected.
Limb-girdle muscular dystrophy type 2E (LGMD-2E) is caused by autosomal recessive defects in the ... more Limb-girdle muscular dystrophy type 2E (LGMD-2E) is caused by autosomal recessive defects in the beta sarcoglycan (SGCB) gene located on chromosome 4q12. In this case report, the clinical findings, histopathological features and molecular genetic data in a boy with β sarcoglycanopathy are presented. An 18-month-old boy had a very high serum creatinine phosphokinase (CPK) level that was accidentally determined. The results of molecular analyses for the dystrophin gene was found to be normal. He underwent a muscle biopsy which showed dystrophic features. Immunohistochemistry showed that there was a total loss of sarcolemmal sarcoglycan complex. DNA analysis revealed a large homozygous deletion in the SCGB gene. During 4 years of follow-up, there was no evidence to predict a severe clinical course except the muscle enzyme elevation and myopathic electromyography (EMG) finding. The presented milder phenotype of LGMD-2E with a large deletion in the SGCB gene provided additional support f...
We report on a 4.5-year-old boy with interstitial monosomy 9p in a unique and complex de novo rea... more We report on a 4.5-year-old boy with interstitial monosomy 9p in a unique and complex de novo rearrangement. The patient had been referred for craniofacial dysmorphism, delayed psychomotor development, and various congenital malformations. We combined cytogenetic studies and FISH analyses to delineate the deletion. The result of our cytogenetic studies was 46,XY,der(9)(p22pter). In order to confirm the deletion, we also performed FISH analysis, which showed that the 9p subtelomeric region was inserted into chromosome 13. Molecular karyotyping was performed to describe the exact genomic breakpoints of the rearrangement. In conclusion, this case is a complex insertion/deletion abnormality which has not been reported before.
Türk Üroloji Dergisi/Turkish Journal of Urology, 2018
Objective: This study was designed to evaluate the prevalence of Human Papilloma Virus (HPV) in s... more Objective: This study was designed to evaluate the prevalence of Human Papilloma Virus (HPV) in semen and document the cycle outcomes in couples with previous intra-cytoplasmic sperm injection (ICSI) failures. Material and methods: One hundred and seventeen couples with at least two ICSI attempts were included in the study. HPV infection in semen and DNA fragmentation in samples were analyzed by commercially available kits. The percentage of spermatozoa with fragmented DNA (DNA fragmentation index: DFI) was determined during fluorescence microscopic examination as previously described. The cycle outcomes of couples with or without HPV infected male partners were recorded. Results: According to our results, the prevalence of HPV was 7.7% in asymptomatic males with at least two previous ICSI failures. The increased DFI (>30%) was observed in 82.9% of the cases. In HPV-positive cases significantly lower number of good quality embryos were obtained. The implantation and pregnancy rates were similar in infected and non-infected males (p>0.05). The early miscarriage rate was slightly higher in HPV-positive group (33% vs. 10%, p>0.05). Conclusion: In cases with previous ICSI failures, the prevalence of HPV infection in semen is not higher than previously reported infertile populations. The reproductive outcome might be impaired in HPV-positive semen due to lower number of good quality embryos, which needs to be clarified by further large population-based studies.
Next-generation sequencing (NGS) technology is used to evaluate hereditary cancer risks of patien... more Next-generation sequencing (NGS) technology is used to evaluate hereditary cancer risks of patients worldwide; however, information concerning the germline multigene mutational spectrum among patients with breast cancer (BC) with consanguineous marriage (CM) is limited. Therefore, this prospective study aimed to determine the molecular characteristics of patients with BC who were tested with multigene hereditary cancer predisposition NGS panel and to show the effect of CM on cancer-related genes. Patients with BC with or without CM and family history (FH) of BC treated in our breast center were selected according to The National Comprehensive Cancer Network (NCCN) criteria for hereditary BC. In these patients, the analysis of a panel of 33 genes involved in hereditary cancer predisposition was performed after genetic counseling by using NGS. The pathogenic variant (PV) and the variant of uncertain significance (VUS) were found to be 15.8 and 47.4%, respectively. PVs were identified in 10/33 genes in 34 patients; 38.2% in BRCA1/2 genes; 6, 24, and 14% in other high, moderate and low-risk genes, respectively. The CM rate was 17.7% among the 215 patients with BC. The PV rate was 13.2% in patients with CM and 16.4% in patients without CM (P=0.80). When PV and VUS were evaluated together, the PV+VUS ratio was significantly higher in patients with CM and FH of BC than patients without CM and FH of BC (88.2 vs. 63.3%, P=0.045). Analysis of multigene panel provided 9.76% additional PVs in moderate/low-risk genes. The PV rate was similar in patients with BC with or without CM. A high PV+VUS ratio in patients with CM and FH of BC suggests that genes whose importance are unknown are likely to be pathogenic genes later.
Ajlan Tukun, MD, PhD, Prof. Medical Genetics. Current Institution: Duzen Laboratories, Ankara, aj... more Ajlan Tukun, MD, PhD, Prof. Medical Genetics. Current Institution: Duzen Laboratories, Ankara, [email protected] (orcid.org/0000-00017445-0918) Abstract Purpose: Infertility is one of the most common health problems affecting about one of five couples, and male factor contributes to a considerable proportion of this condition. This study aimed to detect DNA copy number variations of azoospermic males by high resolution comparative genomic hybridization and suggest candidate chromosomal loci associated with male infertility. Materials and methods: By using Comparative Genomic Hybridization (CGH), we aimed to detect previously unidentified genetic etiologic factors among infertile males. Thus it may be possible to explain some idiopathic cases and provide more accurate counselling to the affected couples. This technique may also allow predicting de novo infertility related loci. Results: A total of 90 patients were analyzed by comparative genomic hybridization. 49 patients revealed...
Cancer biomarkers : section A of Disease markers, 2021
BACKGROUND Due to the heterogeneous nature of Diffuse Large B-cell Lymphoma (DLBCL), the mechanis... more BACKGROUND Due to the heterogeneous nature of Diffuse Large B-cell Lymphoma (DLBCL), the mechanisms underlying tumor development and progression have not yet been fully elucidated. OBJECTIVE This study aimed to compare the characteristics of plasma exosomes of DLBCL patients and healthy individuals and to evaluate the exosomal interactions between DLBCL cell lines and normal B-cells. METHODS Exosome isolation was performed using an ultracentrifugation-based protocol from plasma of 20 patients with DLBCL and 20 controls. The expression of miRNAs from exosome samples was analyzed using a miRNA expression microarray. The presence of exosome-mediated communication between the lymphoma cells and normal B-cells was determined by the co-culture model. RESULTS A significant increase in plasma exosome concentrations of DLBCL patients was observed. There was also a significant decrease in the expression of 33 miRNAs in plasma exosomes of DLBCL patients. It was determined that normal B-cells i...
In this research, a simple method was used to synthesize poly(aniline-co-m-aminobenzoic acid) als... more In this research, a simple method was used to synthesize poly(aniline-co-m-aminobenzoic acid) also known as P(ANI-co-m-ABA) composite polystyrene (PS) nanofibers by using in situ chemical polymerization technique. The copolymer was polymerized on electrospun PS nanofibers mats with varied monomers solution concentration and the polymerization time. P(ANI-co-m-ABA) was also polymerized on PS films were prepared for comparison. The conductivity of the composites was studied and the result showed addition of graphene (GP) into the composites improved the conductivity of the composites. The composites of P(ANI-co-m-ABA)/PS nanofibers and films were characterized by Fourier transform infra-red (FTIR), thermogravimetric analysis (TGA) and ultraviolet visible (UV-vis) spectroscopy. Surface morphology of the composite was studied by scanning electron microscopy (SEM).
Journal of Pediatric Endocrinology and Metabolism, 2021
Objectives Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant condition cau... more Objectives Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant condition caused by heterozygous gain-of-function mutations in the human ALB gene. Case presentation We report, a three-year-old boy with FDH due to p.R242P (or p.R218P without signal peptide) mutation in the ALB gene with a phenotype characterized by extremely high serum total and free thyroxine concentrations. His parents had normal thyroid function tests (TFT), so the mutation detected in this patient is assumed “de novo”. Although the most frequent variant was p.R242H in Caucasians and p.R242P in Japanese, our patient had p.R242P variant. Conclusions Early identification of FDH is fundamental to prevent unnecessary repeats of TFT with different methods. We encourage the ALB gene hot spot sequencing initially and indicate that this molecular diagnosis is a rapid and simple method to diagnose FDH in individuals with euthyroid hyperthyroxinemia.
Pituitary-specific paired-like homeodomain transcription factor, PROP1, is associated with multip... more Pituitary-specific paired-like homeodomain transcription factor, PROP1, is associated with multiple pituitary hormone deficiency. Alteration of the gene encoding the PROP1 may affect somatotropes, thyrotropes, and lactotropes, as well as gonadotropes and corticotropes. We performed genetic analysis of PROP1 gene in a Turkish pedigree with three siblings who presented with short stature. Parents were first degree cousins. Index case, a boy, had somatotrope, gonadotrope, thyrotrope, and corticotrope deficiency. However, two elder sisters had somatotroph, gonadotroph, and thyrotroph deficiency and no corticotroph deficiency. On pituitary magnetic resonance, partial empty sella was detected with normal bright spot in all siblings. In genetic analysis, we found a gross deletion involving PROP1 coding region. In conclusion, we report three Turkish siblings with a gross deletion in PROP1 gene. Interestingly, although little boy with combined pituitary hormone deficiency has adrenocorticotr...
Recombinant chromosome 4 is a very rare chromosomal aberration with eighteen cases reported in th... more Recombinant chromosome 4 is a very rare chromosomal aberration with eighteen cases reported in the literature up to date. Here we report a five years old male patient with de novo rec(4) dup(4p) del(4q). The physical examination findings were as follows: caput quadratum, flat occiput, low frontal hairline, hypertelorism, ptosis, blepharophimosis, high arched eyebrows, flat nasal root with anteverted nostrils and short nose, long and smooth philtrum, thin upper lip with triangular mouth, microretrognathia, high arched palate, dental anomalies, large low-set ears, short neck, broad chest with widely spaced nipples, micropenis, cryptorchidism. Conventional cytogenetic analysis revealed the karyotype as 46,XY,rec(4)dup(4p14p16.3)del(4q34.3q35). Flourescence insitu hybridization (FISH) analysis with sub-telomeric probes for 4p and 4q showed duplication of 4p and deletion of 4q in recombinant chromosome 4. His parents' chromosomal analysis and sub-telomeric FISH analysis were both normal. The patient's final karyotype was reported as 46,XY,rec(4)dup(4p16.3p14)del(4q34.4q35).arr[h g19]4p16.3p14(68,345-36,018)x3,4q34.3q35(177,676,319-190,957,460)x1 detected by Microarray. According the literature all cases with recombinant chromosome 4 have similar clinical findings. Except for our case only one case in the literature has been reported to be de novo. In conclusion, we reported a very rare case of recombinant chromosome 4, which has the largest deletion and duplication in the literature. Further cases with similar findings would help the delineation of the findings associated with this chromosomal abnormality.
Amac: Infertilite, bes ciftten birini etkileyen, en yaygin saglik sorunlarindan biridir. Erkek fa... more Amac: Infertilite, bes ciftten birini etkileyen, en yaygin saglik sorunlarindan biridir. Erkek faktoru, bu durumun onemli bir kismini olusturur. Bu calismanin amaci, azoospermik erkeklerde karsilastirmali genomik hibridizasyon yontemi ile DNA kopya sayisi varyasyonlarinin ve aday kromozomal lokuslarin belirlenmesidir. Gerec ve Yontem: Bu calismada karsilastirmali Genomik Hibridizasyon (CGH) yontemiyle infertil erkeklerde daha once tanimlanamayan genetik etiyolojik faktorleri saptamayi amacladik. Dolayisiyla bazi idiyopatik vakalari aciklamak ve etkilenen ciftlere daha dogru danismanlik saglamak mumkun olabilir. Bu teknik ayni zamanda de novo infertiliteye iliskin lokuslerin tahmin edilmesine izin verebilecektir. Bulgular: Toplam 90 hasta karsilastirmali genomik hibridizasyon ile analiz edildi. 49 hasta en az bir bulgu ortaya cikarirken, 41 hastada (% 46) teknigimizle saptanan kopya sayisi degisimi yoktu. CNV lokuslarinda toplam 21 spermatogenez ile ilgili gen mevcuttu. Sonuc: Calismadan elde edilen veriler, infertil erkeklerin geleneksel yontemlerle saptanamayacak bazi DNA kopya sayisi varyasyonlari gosterebildiklerini gostermektedir. Ek verilerle, bu varyasyonlarin etyolojik onemini saptamak mumkun olabilir.
Presentación de casos clínicos RESUMEN El síndrome tricorrinofalángico (STRF) tipo II (sinónimo: ... more Presentación de casos clínicos RESUMEN El síndrome tricorrinofalángico (STRF) tipo II (sinónimo: síndrome de Langer-Giedion) es un síndrome autosómico dominante raro que afecta genes adyacentes y que se produce como resultado de una microdeleción que abarca los genes EXT1 y TRPS1 en la banda 8q24 (OMIM 150230). En este síndrome se combinan características de dos trastornos autosómicos dominantes: el síndrome tricorrinofalángico tipo I (OMIM 190350) y la osteocondromatosis múltiple hereditaria tipo I (OMIM 133700). El STRF tipo II se caracteriza por escaso cabello, nariz prominente y de extremo bulboso, surco nasolabial plano y alargado, epífisis de las falanges en forma de cono, retraso de la edad ósea durante la infancia y osteocondromas cartilaginosos múltiples. En este artículo presentamos el caso de un paciente de Turquía con las características clínicas y los signos óseos del STRF tipo II en el que se detectó una deleción de 13,8 Mb en las bandas 8q23.1-8q24.13. Palabras clave: síndrome tricorrinofalángico tipo II, deleción cromosómica, baja estatura.
Background: Glutaric aciduria type 1 (GA1) is a rare autosomal recessive neurometabolic disorder ... more Background: Glutaric aciduria type 1 (GA1) is a rare autosomal recessive neurometabolic disorder caused by mutations in the glutaryl CoA dehydrogenase gene (GCDH). If left untreated, it leads to accumulation of neurotoxic metabolites leading to poor neurological outcomes characterized by encephalopathic crises, subdural effusions and extrapyramidal features. Case presentation: We hereby report a consanguineous Sudanese family in which the father and two children were affected whilst the mother was an asymptomatic carrier. All had a novel guanine insertion in position c.1173_1174 (c.1173dupG), resulting in a frame shift and a stop codon downstream (p.Asn392Glufs4X). Conclusion: To our knowledge, this GCDH variant has not been previously reported. Genetic testing should be made widely available in communities where consanguinity is prevalent. This will allow detection of new pathogenic gene variants.
Trichorhinophalangeal syndrome type II (TRPSII) (synonym: Langer-Giedon syndrome) is a rare autos... more Trichorhinophalangeal syndrome type II (TRPSII) (synonym: Langer-Giedon syndrome) is a rare autosomal dominant contiguous gene syndrome, resulting from a microdeletion encompassing the EXT1 and the TRPS1 gene at 8q24 (MIM#150230). This syndrome combines the clinical features of two autosomal dominant disorders, trichorhinophalangeal syndrome type I (MIM#190350) and hereditary multiple osteochondromas type I (MIM # 133700). TRPSII is characterized by sparse scalp hair, a long nose with a bulbous tip, long flat philtrum, cone-shaped epiphyses of the phalanges, retarded bone age in infancy and multiple cartilaginous osteochondromas. We report a Turkish patient who had the clinical features and skeletal signs of TRPSII in whom a 13.8Mb deletion in 8q23.1- 8q24.13 was detected.
Limb-girdle muscular dystrophy type 2E (LGMD-2E) is caused by autosomal recessive defects in the ... more Limb-girdle muscular dystrophy type 2E (LGMD-2E) is caused by autosomal recessive defects in the beta sarcoglycan (SGCB) gene located on chromosome 4q12. In this case report, the clinical findings, histopathological features and molecular genetic data in a boy with β sarcoglycanopathy are presented. An 18-month-old boy had a very high serum creatinine phosphokinase (CPK) level that was accidentally determined. The results of molecular analyses for the dystrophin gene was found to be normal. He underwent a muscle biopsy which showed dystrophic features. Immunohistochemistry showed that there was a total loss of sarcolemmal sarcoglycan complex. DNA analysis revealed a large homozygous deletion in the SCGB gene. During 4 years of follow-up, there was no evidence to predict a severe clinical course except the muscle enzyme elevation and myopathic electromyography (EMG) finding. The presented milder phenotype of LGMD-2E with a large deletion in the SGCB gene provided additional support f...
We report on a 4.5-year-old boy with interstitial monosomy 9p in a unique and complex de novo rea... more We report on a 4.5-year-old boy with interstitial monosomy 9p in a unique and complex de novo rearrangement. The patient had been referred for craniofacial dysmorphism, delayed psychomotor development, and various congenital malformations. We combined cytogenetic studies and FISH analyses to delineate the deletion. The result of our cytogenetic studies was 46,XY,der(9)(p22pter). In order to confirm the deletion, we also performed FISH analysis, which showed that the 9p subtelomeric region was inserted into chromosome 13. Molecular karyotyping was performed to describe the exact genomic breakpoints of the rearrangement. In conclusion, this case is a complex insertion/deletion abnormality which has not been reported before.
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Papers by Kanay Yararbas