[Variant analysis for a pedigree affected with limb-girdle muscular dystrophy type 2D]

Area of Science:

• Genetics
• Molecular Biology
• Neurology

Background:

• Limb-girdle muscular dystrophy type 2D (LGMD2D) is a rare inherited neuromuscular disorder.
• Accurate genetic diagnosis is crucial for patient management and family planning.

Purpose of the Study:

• To identify the genetic cause of LGMD2D in a Chinese family.
• To analyze variants in the SGCA gene using whole exome sequencing (WGS).

Main Methods:

• Excluded mutations in the DMD gene using multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing.
• Performed WGS on the proband and parents to detect variants.
• Validated identified variants using Sanger sequencing.

Main Results:

• No pathogenic variants were found in the DMD gene.
• The proband carried compound heterozygous missense variants in the SGCA gene: c.409G>A (p.Glu137Lys) and c.409G>C (p.Glu137Gln).
• These variants were inherited from the mother and father, respectively, and absent in cord blood DNA.

Conclusions:

• The identified compound heterozygous SGCA variants are likely causative of LGMD2D in this patient.
• This genetic finding facilitates accurate diagnosis, genetic counseling, and prenatal diagnosis for the family.