Mutations in GJB2 (connexin26) are associated with skin disorders and deafness.The Clouston syndrome (MIM129500) is associated with mutations in GJB6 (connexin30).Here, we describe a patient suffering from a Clouston-...Mutations in GJB2 (connexin26) are associated with skin disorders and deafness.The Clouston syndrome (MIM129500) is associated with mutations in GJB6 (connexin30).Here, we describe a patient suffering from a Clouston-syndrome-like phenotype of thin hair, deafness, nail dystrophy, and mild erythrokeratoderma, caused by a novel spontaneous missense mutation in GJB2.The heterozygous mutation in codon 42, AAC > AAG, changes asparagine to lysine (N14K).Interestingly, this asparagine is near two of the residues mutated in Keratitis-like ichthyosis deafness (KID) syndrome (G12R and S17F), yet the phenotype associated with N14K strongly differs from the KID phenotype.Instead, there is clear phenotypic overlapwith syndromes associatedwith connexin26 or 30 mutations.Our findings suggest that careful audiological evaluation of patients suffering from Clouston-syndrome-like phenotypes iswarranted and expand the spectrum of connexin26-associated disease.展开更多
Clouston syndrome(OMIM#129500),also known as hidrotic ectodermal dysplasia type 2,is a rare autosomal dominant skin disorder.To date,four mutations in the GJB6 gene,G11R,V37E,A88V,and D50N,have been confirmed to cause...Clouston syndrome(OMIM#129500),also known as hidrotic ectodermal dysplasia type 2,is a rare autosomal dominant skin disorder.To date,four mutations in the GJB6 gene,G11R,V37E,A88V,and D50N,have been confirmed to cause this condition.In previous studies,the focus has been mainly on gene sequencing,and there has been a lack of research on clinical manifestations and pathogenesis.To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease,we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree.Detailed clinical examination included histopathology,hair microscopy,and scanning electron microscopy.We found a novel heterozygous missense variant(c.134G>C:p.G45A)for Clouston syndrome.We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients’hair under scanning electron microscopy.Our data reveal that a novel variant(c.134G>C:p.G45A)plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.展开更多
Introduction:The gap junction beta 6(GJB6)gene encodes connexin 30.This protein plays critical role in tissues and is responsible for the formation of gap junctions,which have a wide variety of physiological functions...Introduction:The gap junction beta 6(GJB6)gene encodes connexin 30.This protein plays critical role in tissues and is responsible for the formation of gap junctions,which have a wide variety of physiological functions.Disease-associated variants of GJB6 cause non-syndromic hearing loss(HL)and skin lesions.We herein describe a Turkish girl who was diagnosed with HL and in whom genetic analysis revealed a causal variant of GJB6.Case presentation:The 1-year-old girl patient was diagnosed with bilateral HL when she was 1 month old.Apart from this,the patient’s motor/mental development and physical examination were normal.As a result of the analysis with the multi-gene panel,the causative genomic change,c.175G>A(p.Gly59Arg)in the GJB6 gene was determined as heterozygous.Segregation analysis proved the same genotype in the patient’s mother and grandfather.The patient’s mother and grandfather had bilateral HL and palmoplantar hyperkeratosis phenotype.The patient was diagnosed with Clouston syndrome,and genetic counseling was provided to her family.Discussion:Causal variants of GJB6 cause skin manifestations and signs of HL.Molecular diagnosis of these patients is a valuable tool for clinicians in reaching their optimal treatment and clinical management.Conclusion:In syndromic cases in which many organs are affected,the determination of the causative gene is important in directing the patients to appropriate observation,screening,and treatment strategies.展开更多
文摘Mutations in GJB2 (connexin26) are associated with skin disorders and deafness.The Clouston syndrome (MIM129500) is associated with mutations in GJB6 (connexin30).Here, we describe a patient suffering from a Clouston-syndrome-like phenotype of thin hair, deafness, nail dystrophy, and mild erythrokeratoderma, caused by a novel spontaneous missense mutation in GJB2.The heterozygous mutation in codon 42, AAC > AAG, changes asparagine to lysine (N14K).Interestingly, this asparagine is near two of the residues mutated in Keratitis-like ichthyosis deafness (KID) syndrome (G12R and S17F), yet the phenotype associated with N14K strongly differs from the KID phenotype.Instead, there is clear phenotypic overlapwith syndromes associatedwith connexin26 or 30 mutations.Our findings suggest that careful audiological evaluation of patients suffering from Clouston-syndrome-like phenotypes iswarranted and expand the spectrum of connexin26-associated disease.
基金funded by Anhui Provincial Quality Engineering Project of Higher Education Institutions(No.2020jyxm0922)Natural Science Research Project of Higher Education Department of Anhui Province(No.KJ2021A0284)+1 种基金Fund of Anhui Provincial Institute of Translational Medicine(No.2021zhyx-C31)Research Foundation of Anhui Medical University(No.2020xkj154).
文摘Clouston syndrome(OMIM#129500),also known as hidrotic ectodermal dysplasia type 2,is a rare autosomal dominant skin disorder.To date,four mutations in the GJB6 gene,G11R,V37E,A88V,and D50N,have been confirmed to cause this condition.In previous studies,the focus has been mainly on gene sequencing,and there has been a lack of research on clinical manifestations and pathogenesis.To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease,we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree.Detailed clinical examination included histopathology,hair microscopy,and scanning electron microscopy.We found a novel heterozygous missense variant(c.134G>C:p.G45A)for Clouston syndrome.We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients’hair under scanning electron microscopy.Our data reveal that a novel variant(c.134G>C:p.G45A)plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.
文摘Introduction:The gap junction beta 6(GJB6)gene encodes connexin 30.This protein plays critical role in tissues and is responsible for the formation of gap junctions,which have a wide variety of physiological functions.Disease-associated variants of GJB6 cause non-syndromic hearing loss(HL)and skin lesions.We herein describe a Turkish girl who was diagnosed with HL and in whom genetic analysis revealed a causal variant of GJB6.Case presentation:The 1-year-old girl patient was diagnosed with bilateral HL when she was 1 month old.Apart from this,the patient’s motor/mental development and physical examination were normal.As a result of the analysis with the multi-gene panel,the causative genomic change,c.175G>A(p.Gly59Arg)in the GJB6 gene was determined as heterozygous.Segregation analysis proved the same genotype in the patient’s mother and grandfather.The patient’s mother and grandfather had bilateral HL and palmoplantar hyperkeratosis phenotype.The patient was diagnosed with Clouston syndrome,and genetic counseling was provided to her family.Discussion:Causal variants of GJB6 cause skin manifestations and signs of HL.Molecular diagnosis of these patients is a valuable tool for clinicians in reaching their optimal treatment and clinical management.Conclusion:In syndromic cases in which many organs are affected,the determination of the causative gene is important in directing the patients to appropriate observation,screening,and treatment strategies.
