AUTHOR=Chen Xiao-Yu , Song Dan-Yu , Jiang Li , Tan Dan-Dan , Liu Yi-Dan , Liu Jie-Yu , Chang Xing-Zhi , Xing Guo-Gang , Toda Tatsushi , Xiong Hui 

TITLE=Phenotype and Genotype Study of Chinese POMT2-Related α-Dystroglycanopathy

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.692479

DOI=10.3389/fgene.2021.692479

ISSN=1664-8021

ABSTRACT=<sec><title>Objective</title><p>Alpha-dystroglycanopathy (α-DGP) is a subtype of muscular dystrophy caused by defects in the posttranslational glycosylation of α-dystroglycan (α-DG). Our study aimed to summarize the clinical and genetic features of <italic>POMT2</italic>-related α-DGP in a cohort of patients in China.</p></sec><sec><title>Methods</title><p>Pedigrees, clinical data, and laboratory tests of patients diagnosed with <italic>POMT2</italic>-related α-DGP were analyzed retrospectively. The pathogenicity of variants in <italic>POMT2</italic> were predicted by bioinformatics software. The variants with uncertain significance were verified by further analysis.</p></sec><sec><title>Results</title><p>The 11 patients, comprising eight males and three females, were from nine non-consanguineous families. They exhibited different degrees of muscle weakness, ambulation, and intellectual impairment. Among them, three had a muscle-eye-brain disease (MEB)-like phenotype, five presented congenital muscular dystrophy with intellectual disability (CMD-ID), and three presented limb-girdle muscular dystrophy (LGMD). Overall, nine novel variants of <italic>POMT2</italic>, including two non-sense, one frameshift and six missense variants, were identified. The pathogenicity of two missense variants, c.1891G &gt; C and c.874G &gt; C, was uncertain based on bioinformatics software prediction. <italic>In vitro</italic> minigene analysis showed that c.1891G &gt; C affects the splicing of <italic>POMT2</italic>. Immunofluorescence staining with the IIH6C4 antibody of muscle biopsy from the patient carrying the c.874G &gt; C variant showed an apparent lack of expression.</p></sec><sec><title>Conclusion</title><p>This study summarizes the clinical and genetic characteristics of a cohort of <italic>POMT2</italic>-related α-DGP patients in China for the first time, expanding the mutational spectrum of the disease. Further study of the pathogenicity of some missense variants based on enzyme activity detection is needed.</p></sec>