Duchenne muscular dystrophy–like phenotype in an LGMD2I patient with novel FKRP gene variants

Abstract

A 32-year-old man initially received a diagnosis of Duchenne muscular dystrophy (DMD). Genetic analysis revealed two novel heterozygous FKRP variants: c.169G>A (p.Glu57Lys) and c.692G>A (p.Trp231*). These results indicated that the patient had limb-girdle muscular dystrophy type 2I (LGMD2I) caused by recessive FKRP variants. Patients with LGMD2I and DMD have many overlapping phenotypes. LGMD2I should be considered in patients who have a DMD phenotype but not a DMD pathogenic variant.

FKRP mutations cause congenital muscular dystrophy 1C and limb-girdle muscular dystrophy 2I in Asian patients

“…Western blotting using VIA4-1 and GT20ADG was performed in all patients. Western blotting results of Patient 2 and 8 have already been reported [23,24]. The signals detected by VIA4-1 were decreased in all patients.…”

“…Nallamilli et al categorized this mutation as a variant of uncertain significance because it was the only mutation identified in a heterozygous state [28]. Based on ACMG guidelines [41], c.169G>A was considered to be likely pathogenic [24].…”

“…Although all acquired independent walk, three patients lost ambulation by early teenage owing to progressive muscular weakness. Four patients showed a reduction in forced vital capacity and one required non-invasive positive pressure ventilation (NPPV) from the age of 21 years [24]. Three patients showed cardiomyopathy from 14 to 20 years and received pharmacological therapy, including angiotensin-converting enzyme inhibitor and beta-blocker.…”

“…Among the 15 mutations, five were novel and not found in the 1000 Genomes previous stud [23,24]. Heterozygous c.808C>T missense mutation, identified in Patient 1 with MDC1C, was reported to be associated with LGMD2I [25].…”

Diagnostic muscle biopsies in the era of genetics: the added value of myopathology in a selection of limb-girdle muscular dystrophy patients

“…In addition to biochemical evidence of perturbed dystrophin expression, the clinical phenotype of LGMD patients might confound with a dystrophinopathy. The presentation of LGMDR9 may be severe childhood-onset muscle weakness combined with pulmonary and cardiac dysfunction [20].…”