The genetic and clinical features of MORC2 gene-related neuropathy in Chinese patients
Objective To summarize the genetic and phenotypic features of MORC family CW-type zinc finger 2(MORC2)gene-related neuropathy in Chinese patients.Methods The clinical and whole exome sequencing data of MORC2 gene-related neuropathy families with a definitive genetic diagnosis were collected from the Third Xiangya Hospital of Central South University between 2010 and 2023.Literature involving Chinese families with MORC2 gene-related neuropathy was extensively reviewed to provide a comprehensive summary of the genetic and phenotypic spectrum of the disease.Results A total of 10 families with MORC2 gene-related neuropathy were identified and analyzed.Six different heterozygous pathogenic variants in the MORC2 gene were observed among these families,including the novel variant c.1330G＞C(p.G444R)that had not been previously reported.Six families presented as axonal Charcot-Marie-Tooth disease caused by variants in the MORC2 gene(CMT2Z)phenotype with childhood or adult onset,and carried variants c.754C＞T(p.R252W),c.1199A＞G(p.Q400R),c.1330G＞C(p.G444R),or c.1396G＞A(p.D466N);3 families manifested as severe spinal muscular atrophy(SMA)-like phenotype with infantile onset,all carried c.260C＞T(p.S87L);1 family carried c.1181A＞G(p.Y394C),presented as DIGFAN syndrome phenotype with infantile onset combined with mental and motor retardation.Systematic review showed 8 Chinese families carried pathogenic variants of the MORC2 gene,among which 5 families were associated with the CMT2Z phenotype,carrying c.754C＞T(p.R252W),c.1079A＞G(p.E360G),c.1220G＞A(p.C407Y),or c.1397A＞G(p.D466G);1 family was associated with SMA-like phenotype,carrying c.260C＞T(p.S87L);and 2 families were associated with DIGFAN syndrome,carrying c.79G＞A(p.E27K)and c.292G＞A(p.G98R).Conclusions A novel pathogenic variant c.1330G＞C(p.G444R)of the MORC2 gene associated with the CMT2 phenotype is reported.Eleven pathogenic variants of the MORC2 gene have been reported in the Chinese patients to date,and c.754C＞T(p.R252W)may be the most common.Patients with MORC2 gene-related neuropathy carrying different variants present with significant clinical heterogeneity,manifesting as CMT2Z,early-onset severe SMA-like myasthenia,or DIGFAN syndrome.
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