Skip to main content

Genome-wide single nucleotide polymorphism-based autozygosity mapping facilitates identification of mutations in consanguineous families with epidermolysis bullosa.

Author
Abstract
:

Autozygosity mapping (AM) is a technique utilized for mapping homozygous autosomal recessive (AR) traits and facilitation of genetic diagnosis. We investigated the utility of AM for the molecular diagnosis of heterogeneous AR disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this technique to a cohort of 46 distinct EB families using both short tandem repeat (STR) and genome-wide single nucleotide polymorphism (SNP) array-based AM to guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46 cases were diagnosed with homozygous mutations using this method. Independently, 26 cases, including the seven initially unresolved cases, were analyzed with an EB-targeted next-generation sequencing (NGS) panel. NGS identified mutations in five additional cases, initially undiagnosed due to presence of compound heterozygosity, deep intronic mutations, or runs of homozygosity below the set threshold of 2 Mb, for a total yield of 44 out of 46 cases (95.7%) diagnosed genetically. This article is protected by copyright. All rights reserved.

Year of Publication
:
2018
Journal
:
Experimental dermatology
Date Published
:
2018
ISSN Number
:
0906-6705
URL
:
http://dx.doi.org/10.1111/exd.13501
DOI
:
10.1111/exd.13501
Short Title
:
Exp Dermatol
Download citation