Clinical exome sequencing identifies novel compound heterozygous mutations of the POMT2 gene in patients with limb‐girdle muscular dystrophy

Abstract

Objective Mutations in protein O‐mannosyltransferase 2 (POMT2) (MIM#607439) have been identified in severe congenital muscular dystrophy such as Walker–Warburg syndrome (WWS) and milder limb‐girdle muscular dystrophy type 2N (LGMD2N). The aim of this study is to investigate the genetic causes in patients with LGMD2N. Methods Three patients diagnosed with mild limb‐girdle muscular dystrophy were recruited. The genetically pathogenic variant was identified by clinical exome sequencing, and healthy controls were verified by Sanger sequencing. Results Novel compound heterozygous mutations c.800A > G and c.1074_1075delinsAT of POMT2 were revealed in one affected individual by clinical exome sequencing. There was no report of these two variants and predicted to be highly damaging to the function of the POMT2. Conclusion The novel variants extend the spectrum of POMT2 mutations, which promotes the prognostic value of testing for POMT2 mutations in patients with LGMD2N.

Clinical and molecular genetic analysis further delineates the phenotypic variability of POMT2-related limb girdle muscular dystrophy type R14

“…LGMDR14, a rare autosomal recessive subtype of LGMD, is attributed to genetic mutations in the POMT2 gene [4]. Here, we presented a summary of the clinical and genetic characteristics of three Chinese patients with adult-onset LGMDR14.…”

“…As a pivotal molecule, α-DG connects the extracellular matrix and the intracellular actin skeleton,and is indispensable for muscle and nervous system activity [3]. There are approximately 19 pathogenic genes related to α-DGP, which are involved in a wide range of phenotypes [4]. Among them, the POMT2 gene on chromosome 14q24.3 encodes the protein O-mannosyltransferase 2, which is a key enzyme in the glycosylation of α-dystroglycan.…”

“…WWS and CMD patients can present at birth with muscle weakness and severe brain and eye abnormalities, resulting in premature infant death. Conversely, LGMDR14 individuals usually exhibit a mild clinical phenotype, which is characterized by limb-girdle muscle weakness and atrophy [4,7]. Patients may also suffer from mental impairment, gastrocnemius hypertrophy, cardiac involvement and breathing di culties [7,8].…”

“…Few intronic or frameshift mutations were observed. In China, only four cases of LGMDR14 have been documented [4,8].…”

Long-term clinical and MRI follow-up in two POMT2-related limb girdle muscular dystrophy (LGMDR14) patients

“…Hamstrings, paraspinal and glutei are the primarily affected muscles at MRI [3,4]. So far, only 26 patients with LGMDR14 have been clinically described [2][3][4][5][6][7][8][9], and no longitudinal data are available.…”