A novel POMT2 mutation causes mild congenital muscular dystrophy with normal brain MRI

Abstract

We report a patient harboring a novel homozygous mutation of c.604T>G (p.F202V) in POMT2. He showed delayed psychomotor development but acquired the ability to walk at the age of 3 years and 10 months. His brain MRI was normal. No ocular abnormalities were seen. Biopsied skeletal muscle revealed markedly decreased but still detectable glycosylated forms of alpha-dystroglycan (alpha-DG). Our results indicate that mutations in POMT2 can cause a wide spectrum of clinical phenotypes as observed in other genes associated with alpha-dystroglycanopathy. Presence of small amounts of partly glycosylated alpha-DG may have a role in reducing the clinical symptoms of alpha-dystroglycanopathy.

Fig. 1

(A) The patient can stand and walk with no support. Minimal calf hypertrophy is seen. (B) T2 weighted brain magnetic resonance imaging shows no obvious brain anomaly, cortical dysplasia, or white matter changes. (C) Sequence analysis of POMT2 revealed a homozygous mutation at c.604T>G in exon 5.

Fig. 2

(A) Histological analysis. On Hematoxylin and eosin (a) and modified Gomori-trichrime (b) staining, variation in fiber size and scattered necrotic and regenerating fibers are seen. Immunohistochemical analysis using antibodies VIA4-1 (c), which recognize heavily glycosylated form of α-dystroglycan (α—DG), showed greatly reduced sarcolemmal staining in patient, but well-preserved immunoreactivities of β-DG (d) is seen. Bar = 50m. (B) Immunoblotting analysis. Immunoblotting analysis using antibodies of VIA4-1, GT20ADG for α-dystroglycan (α-DG) and laminin overlay assay are performed using skeletal muscle from control (C), Fukuyama-type congenital muscular dystrophy (FCMD; F), and the patient (Pt). VIA4-1 recognizes a broad band about 156 kDa in size in control, and approximately 90kDa in FCMD. In the patient muscle, reduced in size and amount compared with control was observed. GT20ADG revealed bands at approximately 90 kDa in both the patient and FCMD muscles. Laminin overlay assay shows barely detectable band in both the patient and FCMD.