Background. Prolidase deficiency is a complex disease characterized by various skin manifestations accompanied by mental retardation, facial dysmorphism and susceptibility to pyogenic infections. Methods. We assessed ...Background. Prolidase deficiency is a complex disease characterized by various skin manifestations accompanied by mental retardation, facial dysmorphism and susceptibility to pyogenic infections. Methods. We assessed a patient presenting a peculiar phenotype combining manifestations of prolidase deficiency with features typical of hyper-IgE syndrome. Mutation analysis was performed using direct PCR amplification and PCR restriction fragment length polymorphism analysis. Results. We identified a novel homozygous recessive mutation in the PEPD gene, which was found to segregate in the family of the patient with the disease and was not found in a panel of DNA samples representative of all major Druze families living in northern Israel. Discussion. Our results suggest that prolidase deficiency associated with hyper-IgE syndrome, a rare disorder, can be caused by mutations in PEPD.展开更多
The description of various methods for ethnicity classification can be found in the literature, though their reliability still remains unclear. We examined inter-observer agreement in defining the ethnic identificatio...The description of various methods for ethnicity classification can be found in the literature, though their reliability still remains unclear. We examined inter-observer agreement in defining the ethnic identification of patients in a bi-ethnic population (Arab-Jewish) in northern Israel, using place of birth and residence in addition to given and family names. Data about 1006 consecutive patients with acute ischemic stroke were gathered from our stroke registry. The data were analyzed by four independent observers (authors MH, TD, HH, GT) aiming to assign patients either as Arabs or Jews. Agreement between all four observers was excellent, as assessed by Fleiss’ Kappa statistic (κ = 0.96). We conclude that the use of given and family names of patients, together with their place of birth and residence, achieved near-perfect inter-observer agreement and a highly reliable assignment of ethnicity in two large ethnic population groups–Arabs and Jews–in northern Israel.展开更多
Background: Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder characterized by sparse and short scalp hair from birth, followed within a few years by progressive macular degen...Background: Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder characterized by sparse and short scalp hair from birth, followed within a few years by progressive macular degeneration leading to blindness. HJMD was shown to result from mutations in CDH3 encoding P- cadherin. Objectives: In the present study, we attempted to identify the molecular basis of abnormal hair growth in two siblings of Arab Muslim origin with hypotrichosis but no visual symptoms. Methods: Mutation analysis was performed using direct sequencing and polymerase chain reaction- restriction fragment length polymorphism analysis. Results: Patients displayed sparse and short hair since birth. Significant macular degenerative pigmentary changes were noticed in the face of normal visual acuity. Despite the fact that a single CDH3 mutation had previously been described in several families of Israeli Arab Muslim origin, the two affected patients were found to be homozygous carriers of a novel nonsense mutation (Y61 SX) predicted to result in premature termination of P- cadherin translation. Conclusions: The present results indicate that all patients with congenital hypotrichosis should undergo thorough fundus examination, which, when revealing pigmentary macular changes, can be considered as indicative of an underlying CDH3 causative mutation.展开更多
Background: Mutations in genes coding for 2 desmosomal proteins, desmoglein 1 and desmoplakin, have been shown to cause autosomal dominant keratoderma palmoplantaris striata. Observations: We describe a family affecte...Background: Mutations in genes coding for 2 desmosomal proteins, desmoglein 1 and desmoplakin, have been shown to cause autosomal dominant keratoderma palmoplantaris striata. Observations: We describe a family affected with a diffuse nonstriated form of palmoplantar keratoderma. Histopathologic examination of skin biopsy specimens disclosed cell- cell disadhesion in the suprabasal layers of the epidermis, as previously described in keratoderma palmoplantaris striata. We therefore genotyped all family members using microsatellite markers encompassing 3 keratoderma palmoplantaris striata- associated loci. Haplotype analysis suggested linkage of the disease to 18q12.1, which harbors the DSG1 gene, encoding desmoglein 1. Mutation analysis eventually led to the identification of a causative recurrent nonsense mutation in this gene. Conclusions: Mutations in DSG1 are not exclusively associated with striated palmoplantar keratoderma. The present study illustrates the efficacy of an integrative diagnostic approach to palmoplantar keratodermas involving clinical assessment, pathologic examination, microsatellite marker screening, and mutational analysis.展开更多
Congenital recessive ichthyoses represent a vast and markedly heterogeneous group of diseases that have been mapped to at least seven distinct chromosomal loci. In this study, we ascertained two consanguineous familie...Congenital recessive ichthyoses represent a vast and markedly heterogeneous group of diseases that have been mapped to at least seven distinct chromosomal loci. In this study, we ascertained two consanguineous families presenting with congenital ichthyosis. Using homozygosity mapping,we identified a 6.5 cM homozygous region on 12p11.2- q13 shared by all affected individuals. Multipoint logarithmof odds ratio (LOD)- score analysis placed the new locus between markers D12S345 and D12S390 with a maximum LOD score of 4.79 at marker CH12SSR13. This region harbors PPHLN1, encoding periphilin 1, a protein involved in the cornification process. No deleterious mutations were identified within the coding region of this gene, suggesting the existence of another gene associated with epidermal differentiation on 12p11.2- q13.展开更多
文摘Background. Prolidase deficiency is a complex disease characterized by various skin manifestations accompanied by mental retardation, facial dysmorphism and susceptibility to pyogenic infections. Methods. We assessed a patient presenting a peculiar phenotype combining manifestations of prolidase deficiency with features typical of hyper-IgE syndrome. Mutation analysis was performed using direct PCR amplification and PCR restriction fragment length polymorphism analysis. Results. We identified a novel homozygous recessive mutation in the PEPD gene, which was found to segregate in the family of the patient with the disease and was not found in a panel of DNA samples representative of all major Druze families living in northern Israel. Discussion. Our results suggest that prolidase deficiency associated with hyper-IgE syndrome, a rare disorder, can be caused by mutations in PEPD.
文摘The description of various methods for ethnicity classification can be found in the literature, though their reliability still remains unclear. We examined inter-observer agreement in defining the ethnic identification of patients in a bi-ethnic population (Arab-Jewish) in northern Israel, using place of birth and residence in addition to given and family names. Data about 1006 consecutive patients with acute ischemic stroke were gathered from our stroke registry. The data were analyzed by four independent observers (authors MH, TD, HH, GT) aiming to assign patients either as Arabs or Jews. Agreement between all four observers was excellent, as assessed by Fleiss’ Kappa statistic (κ = 0.96). We conclude that the use of given and family names of patients, together with their place of birth and residence, achieved near-perfect inter-observer agreement and a highly reliable assignment of ethnicity in two large ethnic population groups–Arabs and Jews–in northern Israel.
文摘Background: Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder characterized by sparse and short scalp hair from birth, followed within a few years by progressive macular degeneration leading to blindness. HJMD was shown to result from mutations in CDH3 encoding P- cadherin. Objectives: In the present study, we attempted to identify the molecular basis of abnormal hair growth in two siblings of Arab Muslim origin with hypotrichosis but no visual symptoms. Methods: Mutation analysis was performed using direct sequencing and polymerase chain reaction- restriction fragment length polymorphism analysis. Results: Patients displayed sparse and short hair since birth. Significant macular degenerative pigmentary changes were noticed in the face of normal visual acuity. Despite the fact that a single CDH3 mutation had previously been described in several families of Israeli Arab Muslim origin, the two affected patients were found to be homozygous carriers of a novel nonsense mutation (Y61 SX) predicted to result in premature termination of P- cadherin translation. Conclusions: The present results indicate that all patients with congenital hypotrichosis should undergo thorough fundus examination, which, when revealing pigmentary macular changes, can be considered as indicative of an underlying CDH3 causative mutation.
文摘Background: Mutations in genes coding for 2 desmosomal proteins, desmoglein 1 and desmoplakin, have been shown to cause autosomal dominant keratoderma palmoplantaris striata. Observations: We describe a family affected with a diffuse nonstriated form of palmoplantar keratoderma. Histopathologic examination of skin biopsy specimens disclosed cell- cell disadhesion in the suprabasal layers of the epidermis, as previously described in keratoderma palmoplantaris striata. We therefore genotyped all family members using microsatellite markers encompassing 3 keratoderma palmoplantaris striata- associated loci. Haplotype analysis suggested linkage of the disease to 18q12.1, which harbors the DSG1 gene, encoding desmoglein 1. Mutation analysis eventually led to the identification of a causative recurrent nonsense mutation in this gene. Conclusions: Mutations in DSG1 are not exclusively associated with striated palmoplantar keratoderma. The present study illustrates the efficacy of an integrative diagnostic approach to palmoplantar keratodermas involving clinical assessment, pathologic examination, microsatellite marker screening, and mutational analysis.
文摘Congenital recessive ichthyoses represent a vast and markedly heterogeneous group of diseases that have been mapped to at least seven distinct chromosomal loci. In this study, we ascertained two consanguineous families presenting with congenital ichthyosis. Using homozygosity mapping,we identified a 6.5 cM homozygous region on 12p11.2- q13 shared by all affected individuals. Multipoint logarithmof odds ratio (LOD)- score analysis placed the new locus between markers D12S345 and D12S390 with a maximum LOD score of 4.79 at marker CH12SSR13. This region harbors PPHLN1, encoding periphilin 1, a protein involved in the cornification process. No deleterious mutations were identified within the coding region of this gene, suggesting the existence of another gene associated with epidermal differentiation on 12p11.2- q13.
