Cherubism is an autosomal dominant disorder that may
be related to tooth development and eruption... more Cherubism is an autosomal dominant disorder that may be related to tooth development and eruption. It is a disorder of age-related bone remodeling, mostly limited to the maxilla and the mandible, with loss of bone in the jaws and its replacement with large amounts of fibrous tissue. We have used a genomewide search with a three-generation family and have established linkage to chromosome 4p16. Three other families affected with cherubism were also genotyped and were mapped to the same locus. The combined LOD score is 4.21 at a recombination fraction of 0, and the locus spans an interval of »22 cM.
Ectodermal dysplasias caused by mutations in the TP63 gene comprise a group of disorders characte... more Ectodermal dysplasias caused by mutations in the TP63 gene comprise a group of disorders characterized by a spectrum of ectodermal changes, orofacial clefting, and split hand or foot malformation. We report on a boy with a mutation located in the DNA-binding domain of the TP63 gene with atypical phenotype. These data provide additional evidence of the great variability seen in TP63-related disorders and further delineation of genotype-phenotype correlations.
International journal of pediatric otorhinolaryngology, 2009
Noonan syndrome is a mostly autosomal dominant inherited disorder, which can be accompanied by he... more Noonan syndrome is a mostly autosomal dominant inherited disorder, which can be accompanied by hearing disorders or deafness, coagulation disorders, combined heart defects and developmental disorders. We are reporting on two children with an established Noonan syndrome with a severe bilateral hearing loss of respectively 95 and 100 dB and proper findings in the CT/MRI of the petrous bone. After complete otologic and radiologic diagnostics, both children underwent bilateral cochlear implantation successfully. According to the authors' knowledge, this is the first time that cochlear implant therapy is discussed in patients with Noonan syndrome.
Zusammenfassung Hintergrund. Cherubismus ist eine seltene genetisch bedingte Erkrankung der Knoch... more Zusammenfassung Hintergrund. Cherubismus ist eine seltene genetisch bedingte Erkrankung der Knochen, die fast ausschließlich den Ober- und Unterkiefer betrifft. Fallbericht. Wir berichten über 3 männliche Patienten aus 3 aufeinander folgenden Generationen in Familie A und 10 betroffene Patienten in der Familie B. Beim jüngsten Patienten der Familie A fand sich neben dem Cherubismussyndrom eine Kraniosynostose. Der Vater und der Großvater
Congenital central hypoventilation syndrome (CCHS), a rare disorder typically presenting in the n... more Congenital central hypoventilation syndrome (CCHS), a rare disorder typically presenting in the newborn period, results in over 90% of cases from PHOX2B polyalanine repeat mutations. It is characterized by alveolar hypoventilation, symptoms of autonomic nervous system dysregulation, and in a subset of cases Hirschsprung’s disease and, later, tumors of neural crest origin. We describe a preterm infant with severe phenotype
Cherubism (MIM 118400) is an autosomal dominant inherited syndrome characterized by excessive bon... more Cherubism (MIM 118400) is an autosomal dominant inherited syndrome characterized by excessive bone degradation of the upper and lower jaws followed by development of fibrous tissue masses, which causes a characteristic facial swelling. Here we describe seven mutations in the SH3-binding protein SH3BP2 (MIM 602104) on chromosome 4p16.3 that cause cherubism.
Journal of Cancer Research and Clinical Oncology, 2005
Purpose: Germline mutations in either BRCA1 or BRCA2 genes are responsible for the majority of he... more Purpose: Germline mutations in either BRCA1 or BRCA2 genes are responsible for the majority of hereditary breast and ovarian cancers. At present, over thousand distinct BRCA1 and BRCA2 mutations have been identified. Specific mutations are found to be common within particular populations, resulting from genetic founder effects. To investigate the contribution of germline mutations in these two genes to inherited breast cancer in Iran, we performed BRCA1/BRCA2 mutation analyses in ten Iranian high risk breast cancer families. This is the first study analysing the complete coding sequences of both genes that concerns the Iranian population. Methods: BRCA1/BRCA2 mutation detection included sequencing of the coding and the 3¢ and 5¢ untranslated regions. To detect large genomic rearrangements in the BRCA1 gene semi-quantitative multiplex PCR was performed. Results: Two pathogenic mutations in the BRCA2 gene were detected: a novel deletion c.4415_4418delAGAA and a previously described insertion c.6033_6034insGT. In addition, one intronic variation g.5075-53C>T and a deletion/inser-tion g.*381_389del9ins29 in the 3¢ untranslated region of BRCA1 were found in two of the investigated families. Both sequence alterations were absent in an age matched Iranian control group. The BRCA2 homozygous variation p.N372H, previously associated with an increased risk for developing breast cancer, was not identified in this study. We did not detect large genomic rearrangements in BRCA1 in patients tested negatively for disease causing mutations in both genes by standard sequencing. Conclusions: At present, the BRCA2 mutations c.4415_4418delAGAA and c.6033_6034insGT have not been identified in any investigated population except the Iranian. Whether both mutations are specific for the Iranian population or a special subgroup remains to be investigated in larger studies. The absence of BRCA1 mutations in the analysed families may suggest that penetrance or prevalence of BRCA1 mutations may be lower in Iran.
An ocean surface current radar (OSCR) in the very high frequency (VHF) mode was deployed in South... more An ocean surface current radar (OSCR) in the very high frequency (VHF) mode was deployed in South Florida Ocean Measurement Center (SFOMC) during the summer of 1999. During this period, a 29-d continuous time series of vector surface currents was acquired starting on 9 July 1999 and ending 7 August 1999. Over a 20-min sample interval, the VHF radar mapped coastal ocean currents over a 7.5 km 8 km domain with a horizontal resolution of 250 m at 700 grid points. A total of 2078 snapshots of the two-dimensional current vectors were acquired during this time series and of these samples, only 69 samples (3.3%) were missing from the time series. During this period, complex surface circulation patterns were observed that included coherent, submesoscale vortices with diameters of 2 to 3 km inshore of the Florida Current. Comparisons to subsurface measurements from moored and ship-board acoustic Doppler current profiles revealed regression slopes of close to unity with biases ranging from 4 to 8 cm s 1 between surface and subsurface measurements at 3 to 4 m beneath the surface. Correlation coefficients were 0.8 or above with phases of 10 to 20 suggestive of an anticylconic veering of current with depth relative to the surface current. The radar-derived surface current field provided spatial context for an observational network using mooring-, shipand autonomous underwater vehicle-sensor packages that were deployed at the SFOMC.
Neurofibromatosis type 1 is a clinically variable disorder caused mostly by small mutations withi... more Neurofibromatosis type 1 is a clinically variable disorder caused mostly by small mutations within the NF1 gene on chromosome 17q11.2. We used Single Strand Conformation Polymorphism (SSCP) and radioactive sequencing to screen NF1 exons 28 and 29 from 118 unrelated patients, diagnosed with NF1 according to the NIH criteria, identifying five novel and one recurrent germline mutations, two novel polymorphisms and a variant base exchange. All but one cause protein truncation and represent typical NF1 mutations. There are reports that NF1 patients with mutations in exons 28 and 29 could be at greater risk of developing myeloid leukemia. This question was given consideration in this investigation, but none of the children involved have yet shown any symptoms of myeloid leukemia. 4 out of the 6 mutations were de novo.
We screened a total of 92 unrelated patients with neurofibromatosis type 1 (NF1) for mutations in... more We screened a total of 92 unrelated patients with neurofibromatosis type 1 (NF1) for mutations in exon 37 of the NF1 gene, by using temperature gradient gel electrophoresis. Two novel mutations were found: a 4 bp deletion in a so-called quasi-symmetric element (6789del-TTAC) and a recurrent nonsense mutation, which was identified in two unrelated patients, at codon 2264 (C6792A). The independent origin of the latter mutation in two families was confirmed by haplotype analysis. The nonsense mutation and the 4 bp deletion are both predicted to lead to a truncated protein product lacking the Cterminal 20% (aproximately) of its sequence. The occurrence of three independent mutations among 92 NF1 patients at codons 2263-2264 (exon 37) suggests that a specific search for mutations in this area should be undertaken in screening programs for NF1 mutations.
... Hum Genet 92:429430 Lazaro C, Gaona A, Estivill X (1994) Two CA/GT repeat polymor-phisms in ... more ... Hum Genet 92:429430 Lazaro C, Gaona A, Estivill X (1994) Two CA/GT repeat polymor-phisms in intron 27 of the human neurofibromatosis type 1 (NF1) gene. Hum Genet 93:351352 Legius E, Marchuk DA, Collins FS, Glover TW (1993) Somatic deletion of the ...
Neurofibromatosis type 1 (NF1) is caused by NF1 gene mutations. The phenotype is highly variable,... more Neurofibromatosis type 1 (NF1) is caused by NF1 gene mutations. The phenotype is highly variable, with 'modifiers' being discussed as potential determinants. Mismatch repair deficiency was shown to cause NF1 mutations, but constitutional mutation of mismatch repair genes was identified only once in a NF1 patient. We aimed to analyze whether DNA methylation of mismatch repair gene promoters, known to lead to transcriptional silencing, is associated with increased tumor load in NF1 defined by the number of cutaneous neurofibromas. Leukocyte DNA of 79 controls and 79 NF1 patients was investigated for methylation of mismatch repair genes MLH1, MSH2, MSH6, and PMS2 by methylation-specific PCR and pyrosequencing. MLH1, MSH6, and PMS2 promoters were not methylated. By contrast, we found promoter methylation of MSH2 with a higher rate of methylation in NF1 patients compared with controls. Furthermore, when comparing NF1 patients with a low vs those with a high number of cutaneous neurofibromas, MSH2 promoter methylation was significantly different. In patients with a high tumor burden, methylation of two (out of six) CpGs was enhanced. This finding was not confounded by age. In conclusion, enhanced methylation involving transcription start points of mismatch repair genes, such as MSH2 in NF1, has not been described so far. Methylation-induced variability of MSH2 gene expression may lead to variable mismatch repair capacity. Our results may point toward a role of MSH2 as a modifier for NF1, although the amount of DNA methylation and subsequent gene expression in other cell types of NF1 patients needs to be elucidated.
Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorde... more Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorders caused by mutations in genes encoding various components of the RAS-MAPK signaling cascade. NS is associated with mutations in the genes PTPN11, SOS1, RAF1, or KRAS, whereas CFCS can be caused by mutations in BRAF, MEK1, MEK2, or KRAS. The NS phenotype is rarely accompanied by multiple giant cell lesions (MGCL) of the jaw (Noonan-like/MGCL syndrome (NL/MGCLS)). PTPN11 mutations are the only genetic abnormalities reported so far in some patients with NL/MGCLS and in one individual with LEOPARD syndrome and MGCL. In a cohort of 75 NS patients previously tested negative for mutations in PTPN11 and KRAS, we detected SOS1 mutations in 11 individuals, four of whom had MGCL. To explore further the relevance of aberrant RAS-MAPK signaling in syndromic MGCL, we analyzed the established genes causing CFCS in three subjects with MGCL associated with a phenotype fitting CFCS. Mutations in BRAF or MEK1 were identified in these patients. All mutations detected in these seven patients with syndromic MGCL had previously been described in NS or CFCS without apparent MGCL. This study demonstrates that MGCL may occur in NS and CFCS with various underlying genetic alterations and no obvious genotype -phenotype correlation. This suggests that dysregulation of the RAS-MAPK pathway
Robinow syndrome comprises dysmorphic facial features, short stature, brachymesomelia, segmental ... more Robinow syndrome comprises dysmorphic facial features, short stature, brachymesomelia, segmental spine defects, and genital hypoplasia. The range of severity in this disorder is broad. We report on the clinical and molecular findings of two sib pairs from the same extended family with Robinow syndrome due to a novel intragenic ROR2 deletion involving exons 6 and 7 that could not be detected by sequencing. The affected individuals exhibited variability with respect to the cleft lip, cleft palate, and cardiac findings and for the presence in one of the patients of syringomyelia, which has not been previously reported in Robinow syndrome.
We report on three individuals of Muslim Arab origin from a village located in Northern Israel af... more We report on three individuals of Muslim Arab origin from a village located in Northern Israel affected by an apparent autosomal recessive syndrome characterized by distinctive facial phenotype of which the most prominent feature is ocular hypertelorism. The other clinical features of the syndrome include variable degree of mental retardation, genital abnormalities dominated by short penis, and skeletal abnormalities including chest deformity (combination of upper pectus carinatum with lower pectus excavatum), and short palms with broad short fingers. Affected individuals displayed distinctive facial features including upslanting palpebral fissures, thick eyebrows, long philtrum, wide mouth with thin upper lip and upturned corners of the mouth, widow's peak, broad nasal bridge, and simple ears with fleshy overfolded helices. This phenotype does not fully meet typical diagnostic features of any known condition.
Cherubism is an autosomal dominant disorder that may
be related to tooth development and eruption... more Cherubism is an autosomal dominant disorder that may be related to tooth development and eruption. It is a disorder of age-related bone remodeling, mostly limited to the maxilla and the mandible, with loss of bone in the jaws and its replacement with large amounts of fibrous tissue. We have used a genomewide search with a three-generation family and have established linkage to chromosome 4p16. Three other families affected with cherubism were also genotyped and were mapped to the same locus. The combined LOD score is 4.21 at a recombination fraction of 0, and the locus spans an interval of »22 cM.
Ectodermal dysplasias caused by mutations in the TP63 gene comprise a group of disorders characte... more Ectodermal dysplasias caused by mutations in the TP63 gene comprise a group of disorders characterized by a spectrum of ectodermal changes, orofacial clefting, and split hand or foot malformation. We report on a boy with a mutation located in the DNA-binding domain of the TP63 gene with atypical phenotype. These data provide additional evidence of the great variability seen in TP63-related disorders and further delineation of genotype-phenotype correlations.
International journal of pediatric otorhinolaryngology, 2009
Noonan syndrome is a mostly autosomal dominant inherited disorder, which can be accompanied by he... more Noonan syndrome is a mostly autosomal dominant inherited disorder, which can be accompanied by hearing disorders or deafness, coagulation disorders, combined heart defects and developmental disorders. We are reporting on two children with an established Noonan syndrome with a severe bilateral hearing loss of respectively 95 and 100 dB and proper findings in the CT/MRI of the petrous bone. After complete otologic and radiologic diagnostics, both children underwent bilateral cochlear implantation successfully. According to the authors' knowledge, this is the first time that cochlear implant therapy is discussed in patients with Noonan syndrome.
Zusammenfassung Hintergrund. Cherubismus ist eine seltene genetisch bedingte Erkrankung der Knoch... more Zusammenfassung Hintergrund. Cherubismus ist eine seltene genetisch bedingte Erkrankung der Knochen, die fast ausschließlich den Ober- und Unterkiefer betrifft. Fallbericht. Wir berichten über 3 männliche Patienten aus 3 aufeinander folgenden Generationen in Familie A und 10 betroffene Patienten in der Familie B. Beim jüngsten Patienten der Familie A fand sich neben dem Cherubismussyndrom eine Kraniosynostose. Der Vater und der Großvater
Congenital central hypoventilation syndrome (CCHS), a rare disorder typically presenting in the n... more Congenital central hypoventilation syndrome (CCHS), a rare disorder typically presenting in the newborn period, results in over 90% of cases from PHOX2B polyalanine repeat mutations. It is characterized by alveolar hypoventilation, symptoms of autonomic nervous system dysregulation, and in a subset of cases Hirschsprung’s disease and, later, tumors of neural crest origin. We describe a preterm infant with severe phenotype
Cherubism (MIM 118400) is an autosomal dominant inherited syndrome characterized by excessive bon... more Cherubism (MIM 118400) is an autosomal dominant inherited syndrome characterized by excessive bone degradation of the upper and lower jaws followed by development of fibrous tissue masses, which causes a characteristic facial swelling. Here we describe seven mutations in the SH3-binding protein SH3BP2 (MIM 602104) on chromosome 4p16.3 that cause cherubism.
Journal of Cancer Research and Clinical Oncology, 2005
Purpose: Germline mutations in either BRCA1 or BRCA2 genes are responsible for the majority of he... more Purpose: Germline mutations in either BRCA1 or BRCA2 genes are responsible for the majority of hereditary breast and ovarian cancers. At present, over thousand distinct BRCA1 and BRCA2 mutations have been identified. Specific mutations are found to be common within particular populations, resulting from genetic founder effects. To investigate the contribution of germline mutations in these two genes to inherited breast cancer in Iran, we performed BRCA1/BRCA2 mutation analyses in ten Iranian high risk breast cancer families. This is the first study analysing the complete coding sequences of both genes that concerns the Iranian population. Methods: BRCA1/BRCA2 mutation detection included sequencing of the coding and the 3¢ and 5¢ untranslated regions. To detect large genomic rearrangements in the BRCA1 gene semi-quantitative multiplex PCR was performed. Results: Two pathogenic mutations in the BRCA2 gene were detected: a novel deletion c.4415_4418delAGAA and a previously described insertion c.6033_6034insGT. In addition, one intronic variation g.5075-53C>T and a deletion/inser-tion g.*381_389del9ins29 in the 3¢ untranslated region of BRCA1 were found in two of the investigated families. Both sequence alterations were absent in an age matched Iranian control group. The BRCA2 homozygous variation p.N372H, previously associated with an increased risk for developing breast cancer, was not identified in this study. We did not detect large genomic rearrangements in BRCA1 in patients tested negatively for disease causing mutations in both genes by standard sequencing. Conclusions: At present, the BRCA2 mutations c.4415_4418delAGAA and c.6033_6034insGT have not been identified in any investigated population except the Iranian. Whether both mutations are specific for the Iranian population or a special subgroup remains to be investigated in larger studies. The absence of BRCA1 mutations in the analysed families may suggest that penetrance or prevalence of BRCA1 mutations may be lower in Iran.
An ocean surface current radar (OSCR) in the very high frequency (VHF) mode was deployed in South... more An ocean surface current radar (OSCR) in the very high frequency (VHF) mode was deployed in South Florida Ocean Measurement Center (SFOMC) during the summer of 1999. During this period, a 29-d continuous time series of vector surface currents was acquired starting on 9 July 1999 and ending 7 August 1999. Over a 20-min sample interval, the VHF radar mapped coastal ocean currents over a 7.5 km 8 km domain with a horizontal resolution of 250 m at 700 grid points. A total of 2078 snapshots of the two-dimensional current vectors were acquired during this time series and of these samples, only 69 samples (3.3%) were missing from the time series. During this period, complex surface circulation patterns were observed that included coherent, submesoscale vortices with diameters of 2 to 3 km inshore of the Florida Current. Comparisons to subsurface measurements from moored and ship-board acoustic Doppler current profiles revealed regression slopes of close to unity with biases ranging from 4 to 8 cm s 1 between surface and subsurface measurements at 3 to 4 m beneath the surface. Correlation coefficients were 0.8 or above with phases of 10 to 20 suggestive of an anticylconic veering of current with depth relative to the surface current. The radar-derived surface current field provided spatial context for an observational network using mooring-, shipand autonomous underwater vehicle-sensor packages that were deployed at the SFOMC.
Neurofibromatosis type 1 is a clinically variable disorder caused mostly by small mutations withi... more Neurofibromatosis type 1 is a clinically variable disorder caused mostly by small mutations within the NF1 gene on chromosome 17q11.2. We used Single Strand Conformation Polymorphism (SSCP) and radioactive sequencing to screen NF1 exons 28 and 29 from 118 unrelated patients, diagnosed with NF1 according to the NIH criteria, identifying five novel and one recurrent germline mutations, two novel polymorphisms and a variant base exchange. All but one cause protein truncation and represent typical NF1 mutations. There are reports that NF1 patients with mutations in exons 28 and 29 could be at greater risk of developing myeloid leukemia. This question was given consideration in this investigation, but none of the children involved have yet shown any symptoms of myeloid leukemia. 4 out of the 6 mutations were de novo.
We screened a total of 92 unrelated patients with neurofibromatosis type 1 (NF1) for mutations in... more We screened a total of 92 unrelated patients with neurofibromatosis type 1 (NF1) for mutations in exon 37 of the NF1 gene, by using temperature gradient gel electrophoresis. Two novel mutations were found: a 4 bp deletion in a so-called quasi-symmetric element (6789del-TTAC) and a recurrent nonsense mutation, which was identified in two unrelated patients, at codon 2264 (C6792A). The independent origin of the latter mutation in two families was confirmed by haplotype analysis. The nonsense mutation and the 4 bp deletion are both predicted to lead to a truncated protein product lacking the Cterminal 20% (aproximately) of its sequence. The occurrence of three independent mutations among 92 NF1 patients at codons 2263-2264 (exon 37) suggests that a specific search for mutations in this area should be undertaken in screening programs for NF1 mutations.
... Hum Genet 92:429430 Lazaro C, Gaona A, Estivill X (1994) Two CA/GT repeat polymor-phisms in ... more ... Hum Genet 92:429430 Lazaro C, Gaona A, Estivill X (1994) Two CA/GT repeat polymor-phisms in intron 27 of the human neurofibromatosis type 1 (NF1) gene. Hum Genet 93:351352 Legius E, Marchuk DA, Collins FS, Glover TW (1993) Somatic deletion of the ...
Neurofibromatosis type 1 (NF1) is caused by NF1 gene mutations. The phenotype is highly variable,... more Neurofibromatosis type 1 (NF1) is caused by NF1 gene mutations. The phenotype is highly variable, with 'modifiers' being discussed as potential determinants. Mismatch repair deficiency was shown to cause NF1 mutations, but constitutional mutation of mismatch repair genes was identified only once in a NF1 patient. We aimed to analyze whether DNA methylation of mismatch repair gene promoters, known to lead to transcriptional silencing, is associated with increased tumor load in NF1 defined by the number of cutaneous neurofibromas. Leukocyte DNA of 79 controls and 79 NF1 patients was investigated for methylation of mismatch repair genes MLH1, MSH2, MSH6, and PMS2 by methylation-specific PCR and pyrosequencing. MLH1, MSH6, and PMS2 promoters were not methylated. By contrast, we found promoter methylation of MSH2 with a higher rate of methylation in NF1 patients compared with controls. Furthermore, when comparing NF1 patients with a low vs those with a high number of cutaneous neurofibromas, MSH2 promoter methylation was significantly different. In patients with a high tumor burden, methylation of two (out of six) CpGs was enhanced. This finding was not confounded by age. In conclusion, enhanced methylation involving transcription start points of mismatch repair genes, such as MSH2 in NF1, has not been described so far. Methylation-induced variability of MSH2 gene expression may lead to variable mismatch repair capacity. Our results may point toward a role of MSH2 as a modifier for NF1, although the amount of DNA methylation and subsequent gene expression in other cell types of NF1 patients needs to be elucidated.
Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorde... more Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorders caused by mutations in genes encoding various components of the RAS-MAPK signaling cascade. NS is associated with mutations in the genes PTPN11, SOS1, RAF1, or KRAS, whereas CFCS can be caused by mutations in BRAF, MEK1, MEK2, or KRAS. The NS phenotype is rarely accompanied by multiple giant cell lesions (MGCL) of the jaw (Noonan-like/MGCL syndrome (NL/MGCLS)). PTPN11 mutations are the only genetic abnormalities reported so far in some patients with NL/MGCLS and in one individual with LEOPARD syndrome and MGCL. In a cohort of 75 NS patients previously tested negative for mutations in PTPN11 and KRAS, we detected SOS1 mutations in 11 individuals, four of whom had MGCL. To explore further the relevance of aberrant RAS-MAPK signaling in syndromic MGCL, we analyzed the established genes causing CFCS in three subjects with MGCL associated with a phenotype fitting CFCS. Mutations in BRAF or MEK1 were identified in these patients. All mutations detected in these seven patients with syndromic MGCL had previously been described in NS or CFCS without apparent MGCL. This study demonstrates that MGCL may occur in NS and CFCS with various underlying genetic alterations and no obvious genotype -phenotype correlation. This suggests that dysregulation of the RAS-MAPK pathway
Robinow syndrome comprises dysmorphic facial features, short stature, brachymesomelia, segmental ... more Robinow syndrome comprises dysmorphic facial features, short stature, brachymesomelia, segmental spine defects, and genital hypoplasia. The range of severity in this disorder is broad. We report on the clinical and molecular findings of two sib pairs from the same extended family with Robinow syndrome due to a novel intragenic ROR2 deletion involving exons 6 and 7 that could not be detected by sequencing. The affected individuals exhibited variability with respect to the cleft lip, cleft palate, and cardiac findings and for the presence in one of the patients of syringomyelia, which has not been previously reported in Robinow syndrome.
We report on three individuals of Muslim Arab origin from a village located in Northern Israel af... more We report on three individuals of Muslim Arab origin from a village located in Northern Israel affected by an apparent autosomal recessive syndrome characterized by distinctive facial phenotype of which the most prominent feature is ocular hypertelorism. The other clinical features of the syndrome include variable degree of mental retardation, genital abnormalities dominated by short penis, and skeletal abnormalities including chest deformity (combination of upper pectus carinatum with lower pectus excavatum), and short palms with broad short fingers. Affected individuals displayed distinctive facial features including upslanting palpebral fissures, thick eyebrows, long philtrum, wide mouth with thin upper lip and upturned corners of the mouth, widow's peak, broad nasal bridge, and simple ears with fleshy overfolded helices. This phenotype does not fully meet typical diagnostic features of any known condition.
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Papers by Hartmut Peters
be related to tooth development and eruption. It is a
disorder of age-related bone remodeling, mostly limited
to the maxilla and the mandible, with loss of bone in
the jaws and its replacement with large amounts of fibrous
tissue. We have used a genomewide search with
a three-generation family and have established linkage
to chromosome 4p16. Three other families affected with
cherubism were also genotyped and were mapped to the
same locus. The combined LOD score is 4.21 at a recombination
fraction of 0, and the locus spans an interval
of »22 cM.
be related to tooth development and eruption. It is a
disorder of age-related bone remodeling, mostly limited
to the maxilla and the mandible, with loss of bone in
the jaws and its replacement with large amounts of fibrous
tissue. We have used a genomewide search with
a three-generation family and have established linkage
to chromosome 4p16. Three other families affected with
cherubism were also genotyped and were mapped to the
same locus. The combined LOD score is 4.21 at a recombination
fraction of 0, and the locus spans an interval
of »22 cM.