Premium
Autosomal‐dominant WFS1 ‐related disorder—Report of a novel WFS1 variant and review of the phenotypic spectrum of autosomal recessive and dominant forms
Author(s) -
AbuElHaija Aya,
McGowan Caroline,
Vanderveen Deborah,
Bodamer Olaf
Publication year - 2021
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61945
Subject(s) - wolfram syndrome , aunt , cataracts , sensorineural hearing loss , atrophy , medicine , hearing loss , diabetes mellitus , genetics , allele , endocrinology , pediatrics , biology , audiology , gene , sociology , anthropology
Abstract Wolfram syndrome was initially reported as an autosomal recessive (AR), progressive neurodegenerative disorder that leads to diabetes insipidus, childhood onset diabetes mellitus (DM), optic atrophy, and deafness (D) also known as DIDMOAD. However, heterozygous dominant pathogenic variants in Wolfram syndrome type 1 (WFS1) may lead to distinct, allelic conditions, described as isolated sensorineural hearing loss (SNHL), syndromic SNHL, congenital cataracts, or early onset DM. We report a family with a novel dominant, likely pathogenic variant in WFS1 (NM_006005.3) c.2605_2616del12 (p.Ser869_His872del), resulting in cataracts, SNHL, and DM in a female and her mother. A maternal aunt had cataracts, DM, and SNHL but was not tested for the familial WFS1 mutation. Both the mother and maternal aunt had early menopause by age 43 years and infertility which may be a coincidental finding that has not been associated with autosomal dominant AD WFS1 ‐related disorder to the best of our knowledge. Screening at risk individuals in families with the AR Wolfram syndrome, for DM, SNHL, and for cataracts is indicated.