Zalesny Alayna N, Gunter Sarah, Williams Charles A
OU Health Pediatric Specialties Clinic, Oklahoma Children's Hospital, Oklahoma City, Oklahoma, United States.
Division of Genetics and Metabolism, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, United States.
Glob Med Genet. 2024 Oct 16;11(4):344-348. doi: 10.1055/s-0044-1791804. eCollection 2024 Dec.
We report a 7-year-old girl born with pyloric atresia but without congenital epidermolysis bullosa or skin fragility. Nail dysplasia developed at age 8 months and throughout childhood she suffered from onycholysis and mild nail hypertrophy. Whole-exome sequencing demonstrated biallelic mutations in alpha6 integrin (ITGA6): p. Q139* and R153W. ITGA6 normally forms a protein heterodimer with beta4 integrin (ITGB4), and this dimer participates in anchoring the basal skin cells to the extracellular matrix. Biallelic mutations in each gene are well known to cause epidermolysis bullosa and pyloric atresia. However, this child had ostensibly normal skin without any evidence of skin fragility. In a literature search, we identified 11 cases involving ITGA6 mutations, and all had epidermolysis skin changes. Thus, this case adds to the reported phenotype of ITGA6 disease since it is the first to show absence of an epidermolysis bullosa phenotype in the setting of pyloric atresia and nail dysplasia.
我们报告了一名7岁女孩，她出生时患有幽门闭锁，但没有先天性大疱性表皮松解症或皮肤脆弱症。8个月大时出现指甲发育异常，在整个儿童期她都患有甲剥离和轻度指甲肥厚。全外显子组测序显示α6整合素（ITGA6）存在双等位基因突变：p.Q139*和R153W。ITGA6通常与β4整合素（ITGB4）形成蛋白质异二聚体，并且该二聚体参与将基底皮肤细胞锚定到细胞外基质。每个基因的双等位基因突变众所周知会导致大疱性表皮松解症和幽门闭锁。然而，这名儿童的皮肤表面看似正常，没有任何皮肤脆弱的迹象。在文献检索中，我们确定了11例涉及ITGA6突变的病例，所有病例都有表皮松解性皮肤改变。因此，该病例增加了ITGA6疾病的报告表型，因为它是首例在幽门闭锁和指甲发育异常情况下未出现大疱性表皮松解症表型的病例。
