Childhood onset limb-girdle muscular dystrophies in the Aegean part of Turkey

Abstract

The aim of this study is to analyze the epidemiology of the clinical and genetic features of childhood-onset limb-girdle muscular dystrophies (LGMD) in the Aegean part of Turkey. In total fifty-six pediatric cases with LGMD followed in four different pediatric neurology departments in the Aegean region of Turkey were evaluated. Among them, LGMD2C was the most common followed by LGMD2A, LGMD2D, and LGMD2F with equal frequencies. In twenty-eight patients (50%) the diagnosis could be confirmed by genetic analysis, where SGCG proved to be disease-causing in most of the cases. About half of the patients were diagnosed with whole exome or targeted gene sequencing. A positive correlation between muscle biopsy and genetic findings were observed in 11% of the patients. We report one novel frameshifting mutation in TTN. Knowledge on frequencies of childhood-onset limb-girdle muscular dystrophies and related genes in Turkey will lead to a prompt diagnosis of these neuromuscular disorders.

Keywords: Turkey; childhood; genetic diagnosis; limb-girdle muscular dystrophy.

Figure 1.

The muscle biopsy of the patient with the genetically confirmed LGMD2D showing no sign of dystrophy (A) and normal expression of all sarcoglycans (B, C, D, E). The biopsy was taken at the age of 8 years.

Figure 2.

Pedigree of the family with TTN mutation. Homozygous frameshift mutation, g.2:179393311-179393315, c.107163_107167delTACTT, NM_001267550.1, Located in exon 361 of LRG 391_t1, encoding IgG-like domain 150, maps to M-Band in the Sarcomere, reference Sequence with deleted bp kursiv: TCTCTTTACTTGTGAAAT.

Figure 3.

The muscle biopsy of the index patient showed a complete deficiency of dysferlin immunohistochemically (A). The positive simultaneously stained control slide of another patient’s biopsy reveals a complete sarcolemmal staining of the dysferlin antibody (B). There was only one focus with degenerative and regenerative fibers. In this focus, there were also macrophages showing myophagia (C). The muscle biopsy was taken at the age of 17 years from the left quadriceps femoris.