POMT1 – Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2K

In a six-generation consanguineous Han Chinese family, exome and Sanger sequencing identified compound heterozygous POMT1 variants c.1338+1G>A (p.His415LysfsTer3) and c.1457G>C (p.Trp486Ser) co-segregating with a later-onset limb-girdle muscular dystrophy phenotype (LGMD2K) characterised by progressive proximal pelvic and shoulder girdle weakness, joint contractures, intellectual disability, and elevated creatine kinase without structural brain or ocular defects (PMID:28157257). Segregation of both variants in two affected siblings supports autosomal recessive inheritance of LGMD2K.

Functional studies of POMT1 in Walker–Warburg syndrome demonstrate that patient-derived POMT1 truncating mutations abolish protein O-mannosyltransferase activity when co-expressed with POMT2 in Sf9 cells, indicating that loss of POMT1 enzymatic function underlies α-dystroglycan hypoglycosylation and muscle pathology (PMID:15522202).

References

• Journal of Cellular and Molecular Medicine • 2017 • Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy-dystroglycanopathy C1. PMID:28157257
• Biochemical and Biophysical Research Communications • 2004 • Mutations of the POMT1 gene found in patients with Walker-Warburg syndrome lead to a defect of protein O-mannosylation. PMID:15522202

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