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Is PNPT1 ‐related hearing loss ever non‐syndromic? Whole exome sequencing of adult siblings expands the natural history of PNPT1 ‐related disorders
Author(s) -
Eaton Alison,
Bernier Francois P.,
Goedhart Caitlin,
Caluseriu Oana,
Lamont Ryan E.,
Boycott Kym M.,
Parboosingh Jillian S.,
Innes A. Micheil
Publication year - 2018
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.40516
Subject(s) - sensorineural hearing loss , natural history , ataxia , hearing loss , exome sequencing , dystonia , medicine , atrophy , spasticity , pediatrics , family history , phenotype , disease , audiology , genetics , pathology , biology , physical medicine and rehabilitation , gene , psychiatry
PNPT1 is a mitochondrial RNA transport protein that has been linked to two discrete phenotypes, namely isolated sensorineural hearing loss (OMIM 614934) and combined oxidative phosphorylation deficiency (OMIM 614932). The latter has been described in multiple families presenting with complex neurologic manifestations in childhood. We describe adult siblings with biallelic PNPT1 variants identified through WES who presented with isolated severe congenital sensorineural hearing loss (SNHL). In their 40s, they each developed and then followed a nearly identical neurodegenerative course with ataxia, dystonia, and cognitive decline. Now in their 50s and 60s, all have developed the additional features of optic nerve atrophy, spasticity, and incontinence. The natural history of the condition in this family may suggest that the individuals previously reported as having isolated SNHL may be at risk of developing multisystem disease in late adulthood, and that PNPT1 ‐related disorders may constitute a spectrum rather than distinct phenotypes.