Summary:Non-Herlitz junctional epidermolysis bullosa(JEB-nH),an autosomal recessive bullous genodermatosis,is characterized by generalized skin blistering from birth onward,dental anomalies,universal alopecia and nail...Summary:Non-Herlitz junctional epidermolysis bullosa(JEB-nH),an autosomal recessive bullous genodermatosis,is characterized by generalized skin blistering from birth onward,dental anomalies,universal alopecia and nail dystrophy.The underlying defect is mutation of the COLI7AI gene encoding the type XVⅡcollagen,resulting in losing structure for attachment of basal epithelial cells to the matrix.In present study,we described one case of congenitally affected female child aged 10 years,with skin blistering.Dermatologic examination revealed sparse,mild blisters on the face and hand,with profound enamel pitting of the teeth.Skin biopsy from proband's bullous skin displayed subepidermal bulla formation without acantholysis.The immunofluorescence of anti-type XVⅡcollagen antibody staining showed loss of type XVⅡcollagen staining at the basement membrane zone.A combination of whole exome sequencing(WES)and Sanger sequencing revealed the novel heterozygous mutations(C.4324C>T;p.Q1442^*and C.I 834G>C;p.G612R)in COLI7AI gene,which could be associated with the observed JEB-nH.One allele had a novel nonsense mutation(c.4324C>T;p.Q1442^*),resulting in nonsense-mediated mRNA decay and truncated collagen XVⅡ;the other allelc had a novel misscnse mutation of c.1834G>C;p.G612R in exon 22,causing a glycine-to-arginine substitution in the Gly-X-Y triple helical repeating motifs and decreasing the thermal stability of collagen XVⅡ.Our findings indicate that the genetic test based on WES can be useful in diagnosing JEB-nH patients.The novel pathogenic mutations identified would further expand our understanding of the mutation spectrum of COLI7AI gene in association with the inherited blistering diseases.展开更多
To the Editor:Sex chromosomal aneuploidies(SCAs)are common chromosomal aberrations that are normally diagnosed after birth.It results in abnormal physical development or infertility.The prenatal incidence is as high a...To the Editor:Sex chromosomal aneuploidies(SCAs)are common chromosomal aberrations that are normally diagnosed after birth.It results in abnormal physical development or infertility.The prenatal incidence is as high as 1/435 and is usually identified by karyotyping.SCAs are characterized by an abnormal number of sex chromosomes and include monosomy(45,X),trisomy(47,XXX,47,XXY,and 47,XYY),other aneuploidies and various forms of sex chromosome mosaicism.The phenotypes of SCA patients are diverse.The prenatal diagnosis of fetal SCAs affects the parents and there is a need for clinical counseling.What's more,early diagnosis is important as it provides opportunities for early treatment and future healthcare for children with SCAs.展开更多
基金This work was supported by the National Natural Science Foundation of China(No.81700032).
文摘Summary:Non-Herlitz junctional epidermolysis bullosa(JEB-nH),an autosomal recessive bullous genodermatosis,is characterized by generalized skin blistering from birth onward,dental anomalies,universal alopecia and nail dystrophy.The underlying defect is mutation of the COLI7AI gene encoding the type XVⅡcollagen,resulting in losing structure for attachment of basal epithelial cells to the matrix.In present study,we described one case of congenitally affected female child aged 10 years,with skin blistering.Dermatologic examination revealed sparse,mild blisters on the face and hand,with profound enamel pitting of the teeth.Skin biopsy from proband's bullous skin displayed subepidermal bulla formation without acantholysis.The immunofluorescence of anti-type XVⅡcollagen antibody staining showed loss of type XVⅡcollagen staining at the basement membrane zone.A combination of whole exome sequencing(WES)and Sanger sequencing revealed the novel heterozygous mutations(C.4324C>T;p.Q1442^*and C.I 834G>C;p.G612R)in COLI7AI gene,which could be associated with the observed JEB-nH.One allele had a novel nonsense mutation(c.4324C>T;p.Q1442^*),resulting in nonsense-mediated mRNA decay and truncated collagen XVⅡ;the other allelc had a novel misscnse mutation of c.1834G>C;p.G612R in exon 22,causing a glycine-to-arginine substitution in the Gly-X-Y triple helical repeating motifs and decreasing the thermal stability of collagen XVⅡ.Our findings indicate that the genetic test based on WES can be useful in diagnosing JEB-nH patients.The novel pathogenic mutations identified would further expand our understanding of the mutation spectrum of COLI7AI gene in association with the inherited blistering diseases.
基金This work was supported by the grants from the Hubei Province Health and Family Planning Scientific Research Project(No.W J2018H0171)the Natural Science Foundation of Hubei Province(NO.2017CFB271)the Applied Basic Research Programs of Wuhan Science and Technology Departm ent(No.2017060201010200).
文摘To the Editor:Sex chromosomal aneuploidies(SCAs)are common chromosomal aberrations that are normally diagnosed after birth.It results in abnormal physical development or infertility.The prenatal incidence is as high as 1/435 and is usually identified by karyotyping.SCAs are characterized by an abnormal number of sex chromosomes and include monosomy(45,X),trisomy(47,XXX,47,XXY,and 47,XYY),other aneuploidies and various forms of sex chromosome mosaicism.The phenotypes of SCA patients are diverse.The prenatal diagnosis of fetal SCAs affects the parents and there is a need for clinical counseling.What's more,early diagnosis is important as it provides opportunities for early treatment and future healthcare for children with SCAs.
