ClinVar

In 2 unrelated patients with congenital muscular dystrophy and severe mental retardation (MDDGB2; 613156), Yanagisawa et al. (2007) identified a homozygous 1997A-G transition in exon 19 of the POMT2 gene, resulting in a tyr666-to-cys (Y666C) substitution in a highly conserved residue. The patients were of Moroccan and French descent, respectively. Haplotype analysis indicated a founder effect. Two additional patients with a similar phenotype were compound heterozygous for Y666C and another pathogenic POMT2 mutation (W647X; 607439.0005 and W748R; 607439.0006).

Godfrey et al. (2007) identified a homozygous Y666C substitution in 2 sibs with congenital muscular dystrophy and low IQ. Both patients had onset in infancy and increased serum creatine kinase. One achieved walking, the other sitting. One had contractures, muscle hypertrophy, and microcephaly. The other had hypoplastic cerebellum, micropenis, and cryptorchidism.

Godfrey et al. (2007) identified a homozygous Y666C mutation in a patient classified as having muscle-eye-brain disease (MDDGA2; 613150). The patient, who reportedly had onset at age 4 years, never achieved walking, and had increased serum creatine kinase, muscle hypertrophy, microcephaly, low IQ, and encephalocele. Two additional patients with muscle-eye-brain disease were compound heterozygous for Y666C and another pathogenic POMT2 mutation (see, e.g., R413P; 607439.0007).

Mercuri et al. (2009) identified compound heterozygosity for Y666C and G246D (607439.0016) in an Italian patient with congenital muscular dystrophy, microcephaly, mental retardation, but normal brain MRI with minimal white matter changes.

Yanagisawa et al. (2009) reported 3 unrelated French patients who were compound heterozygous for the Y666C mutation and another pathogenic mutation in the POMT2 gene. Two patients with MDDGB2 were compound heterozygous for Y666C and another pathogenic mutation (see, e.g., 607439.0017), whereas the third had the more severe MDDGA2 phenotype and carried Y666C and a deletion of several exons of the POMT2 gene.