A novel FKRP gene mutation in a Taiwanese patient with limb-girdle muscular dystrophy 2I.
Limb-girdle muscular dystrophy (LGMD) is a group of hereditary muscle diseases with preferential involvement of the shoulder and pelvic girdle muscles, but with no pathognomonic features as in facioscapulohumeral and congenital muscular dystrophies. We report 18-year-old female with progressive shoulder and pelvic muscle weakness. She had marked restrictive pulmonary dysfunction. Echocardiogram showed mild decrease in ejection fraction of 52% (normal: >55%). She was first seen in our hospital at age 2 years with progressive proximal muscle weakness and elevated creatine kinase (CK) level to 15,290 IU/L, with what clinically and pathologically appeared to be steroid-responsive inflammatory myopathy. She responded dramatically to steroid therapy. Progressive proximal muscle weakness began again at age 8 years. Serum CK was 14,910 IU/L. She was wheelchair-bound by age 12. Muscle biopsy showed dystrophic changes without inflammation with reduced immunoreactivity to an antibody against sugar chain (VIA4-1) of alpha-dystroglycan. On laminin overlay assay, there was a nearly complete loss of laminin-binding activity to alpha-dystroglycan. Genetic analysis of fukutin-related protein (FKRP) gene revealed a novel compound heterozygous mutation of c.823C>T (p.R275C) and c.948delC, confirming the diagnosis of LGMD2I, the first reported case in East Asia.
Lin
Yi-Ching
YC
Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Murakami
Terumi
T
Hayashi
Yukiko K
YK
Nishino
Ichizo
I
Nonaka
Ikuya
I
Yuo
Chung-Yee
CY
Jong
Yuh-Jyh
YJ
D000293:Adolescent; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D009154:Mutation; D010430:Pentosyltransferases; D011506:Proteins / Q000235:genetics*; D013624:Taiwan
D011506:Proteins; C443107:FKRP protein, human; D010430:Pentosyltransferases