First case report of complete paternal isodisomy of chromosome 10 harbouring a novel variant in COL17A1 that causes junctional epidermolysis bullosa intermediate

BMC Med Genomics. 2022 Jun 18;15(1):136. doi: 10.1186/s12920-022-01285-x.

Abstract

Background: Uniparental disomy (UPD) is a condition in which both chromosomes are inherited from the same parent, except for imprinting disorders. Uniparental isodisomy (UPiD) may result in a homozygous variant contributing to an autosomal recessive disorder in the offspring of a heterozygous carrier. Junctional epidermolysis bullosa intermediate (JEB intermediate) is an autosomal recessive inherited disease that is associated with a series of gene variants, including those of COL17A1.

Case presentation: We report the first case of complete paternal UPiD of chromosome 10 harbouring a novel homozygous variant in COL17A1: c.1880(exon23)delG (p.G627Afs*56). This variant led to the clinical phenotype of junctional epidermolysis bullosa intermediate in a 5-year-old child. Trio-whole exome sequencing (Trio-WES) and in silico data analysis were used for variant identification, Sanger sequencing was performed for variant validation, and pathological examination was performed as the gold standard for phenotype confirmation.

Conclusions: We recommend the use of WES as a first-tier test for the diagnosis of epidermolysis bullosa, especially for paediatric patients. Moreover, UPD events should be detected and analysed routinely through WES data in the future.

Keywords: COL17A1; Case report; Genetic counselling; Junctional epidermolysis bullosa intermediate; Paternal uniparental disomy; Whole exome sequencing.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 10
  • Epidermolysis Bullosa, Junctional* / genetics
  • Epidermolysis Bullosa, Junctional* / pathology
  • Heterozygote
  • Homozygote
  • Humans
  • Uniparental Disomy