[Adhalin gene mutations in malignant limb-girdle muscular dystrophy and clinical features in adhalin-deficient muscular dystrophy].

We have reported adhalin gene mutations in 4 patients from 3 families with malignant limb-girdle muscular dystrophy (MLGMD), and summarized the clinical features in adhalin-deficient muscular dystrophy (ADMD) reported as severe childhood autosomal recessive muscular dystrophy (SCARMD) in the English literatures. Adhalin cDNA amplified from RNA by reverse transcription polymerase chain reaction (RT-PCR) was sequenced in 3 patients from 2 consanguinous families (Wa. and Ta.) with MLGMD who showed immunohistochemically a complete deficiency of adhalin in the skeletal muscle, and adhalin genomic DNA amplified by PCR was sequenced in 1 patient from a non-consanguinous family (Ma.). In one patient from family Wa., a cytosine to thymine substitution at nt. 229 was identified in the adhalin gene, resulting in the replacement of Arg by Cys at codon 77. In two patients from family Ta., an adenine to guanine substitution at nt. 410 and an insertion of 15 bases between nt. 408 and 409 were identified, resulting in Glu to Gly replacement at codon 137 and insertion of a peptide with 5 amino acids. In one patient from family Ma., a deletion of adenine at nt. 404 or nt. 405 and a thymidine to cytosine substitution at nt. 470 were identified. These amino acid replacements are expected to change the secondary and tertiary structure, which may affect the interaction of adhalin with other dystrophin-associated glycoproteins and basal lamina, and may subsequently cause the degeneration of muscle fibers. Sixty-six cases from 49 families with ADMD have been reported in the literature. Compared with patients with Duchenne muscular dystrophy (DMD), patients with ADMD were older in age at the time of onset or loss of ambulation. Mental retardation and cardiac dysfunction were rarely observed in ADMD patients. On muscle histology, the number of necrotic fibers, opaque fibers and regenerative fibers was less in ADMD. ADMD was classified into two groups; complete and incomplete adhalin-deficient. There was no essential difference between the two groups in clinical features and muscle histology, but the former was characterized by more severe clinical features than the latter. ADMD can be caused by various types of mutations in the adhalin gene.