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A complex homozygous mutation in ABHD12 responsible for PHARC syndrome discovered with NGS and review of the literature

2017; Wiley; Volume: 22; Issue: 2 Linguagem: Inglês

10.1111/jns.12216

1529-8027

Justine Lerat, Pascal Cintas, Hélène Beauvais‐Dzugan, Corinne Magdelaine, Franck Sturtz, Anne‐Sophie Lia,

Neuroscience and Neuropharmacology Research

Abstract 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.