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A complex homozygous mutation in ABHD12 responsible for PHARC syndrome discovered with NGS and review of the literature
Author(s) -
Lerat Justine,
Cintas Pascal,
BeauvaisDzugan Hélène,
Magdelaine Corinne,
Sturtz Franck,
Lia AnneSophie
Publication year - 2017
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/jns.12216
Subject(s) - mutation , phenotype , genetics , genotype , medicine , population , biology , pathology , gene , environmental health
PHARC syndrome (MIM612674) is an autosomal recessive neurodegenerative pathology that leads to demyelinating P olyneuropathy, H earing loss, cerebellar A taxia, R etinitis pigmentosa, and early‐onset C ataracts (PHARC). These various symptoms can appear at different ages. PHARC syndrome is caused by mutations in ABHD12 (α‐β hydrolase domain 12), of which several have been described. We report here a new complex homozygous mutation c.379_385delAACTACTinsGATTCCTTATATACCATTGTAGTCTTACTGCTTTTGGTGAACACA (p.Asn127Aspfs*23). This mutation was detected in a 36‐year‐old man, who presented neuropathic symptoms from the age of 15, using a next‐generation sequencing panel. This result suggests that the involvement of ABHD12 in polyneuropathies is possibly underestimated. We then performed a comparative study of other patients presenting ABHD12 mutations and searched for genotype‐phenotype correlations and functional explanations in this heterogeneous population.