Lerat Justine, Cintas Pascal, Beauvais-Dzugan Hélène, Magdelaine Corinne, Sturtz Franck, Lia Anne-Sophie
EA6309 - Neuropathies Périphériques et Maintenance Myélinique, Université de Limoges, Limoges, France.
Service Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, CHU Dupuytren, Limoges, France.
J Peripher Nerv Syst. 2017 Jun;22(2):77-84. doi: 10.1111/jns.12216.
PHARC syndrome (MIM612674) is an autosomal recessive neurodegenerative pathology that leads to demyelinating Polyneuropathy, Hearing loss, cerebellar Ataxia, Retinitis pigmentosa, and early-onset Cataracts (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.
PHARC综合征（MIM612674）是一种常染色体隐性神经退行性病变，可导致脱髓鞘性多发性神经病、听力丧失、小脑共济失调、色素性视网膜炎和早发性白内障（PHARC）。这些不同症状可在不同年龄出现。PHARC综合征由ABHD12（α-β水解酶结构域12）突变引起，其中已有几种突变被描述。我们在此报告一种新的复合纯合突变c.379_385delAACTACTinsGATTCCTTATATACCATTGTAGTCTTACTGCTTTTGGTGAACACA（p.Asn127Aspfs*23）。使用下一代测序面板在一名36岁男性中检测到该突变，该男性自15岁起出现神经病变症状。这一结果表明，ABHD12在多发性神经病中的作用可能被低估。然后，我们对其他存在ABHD12突变的患者进行了一项比较研究，并在这个异质性群体中寻找基因型-表型相关性及功能解释。
