Implication of the SH3TC2 gene in Charcot-Marie-Tooth disease associated with deafness and/or scoliosis: Illustration with four new pathogenic variants.
The autosomal recessive demyelinating form of Charcot-Marie-Tooth can be due to SH3TC2 gene pathogenic variants (CMT4C, AR-CMTde-SH3TC2). We report on a series of 13 patients with AR-CMTde-SH3TC2 among a French cohort of 350 patients suffering from all type of inheritance peripheral neuropathy. The SH3TC2 gene appeared to be the most frequently mutated gene for demyelinating neuropathy in this series by NGS. Four new pathogenic variants have been identified: two nonsense variants (p.(Tyr970*), p.(Trp1199*)) and two missense variants (p.(Leu1126Pro), p.(Ala1206Asp)). The recurrent variant p.Arg954* was present in 62%, and seems to be a founder mutation. The phenotype is fairly homogeneous, as all these patients, except the youngest ones, presented scoliosis and/or hearing loss.
['Lerat|J|J|', 'Magdelaine|C|C|', 'Lunati|A|A|', 'Dzugan|H|H|', 'Dejoie|C|C|', 'Rego|M|M|', 'Beze Beyrie|P|P|', 'Bieth|E|E|', 'Calvas|P|P|', 'Cintas|P|P|', 'Delaubrier|A|A|', 'Demurger|F|F|', 'Gilbert-Dussardier|B|B|', 'Goizet|C|C|', 'Journel|H|H|', 'Laffargue|F|F|', 'Magy|L|L|', 'Taithe|F|F|', 'Toutain|A|A|', 'Urtizberea|J A|JA|', 'Sturtz|F|F|', 'Lia|A S|AS|']
D000328:Adult D000368:Aged D002607:Charcot-Marie-Tooth Disease D002648:Child D015331:Cohort Studies D003638:Deafness D005260:Female D005602:France D014644:Genetic Variation D006801:Humans D047908:Intracellular Signaling Peptides and Proteins D008297:Male D008875:Middle Aged D009154:Mutation D012600:Scoliosis D055815:Young Adult
SH3TC2 Charcot-Marie-Tooth Scoliosis Neuropathy NGS Hearing loss