Diagnosis and genetic testing analysis of limb-girdle muscular dystrophy type 2U caused by a compound heterozygous mutation in the ISPD gene.

Limb-girdle muscular dystrophy (LGMD), a rare group of non-congenital inherited muscle diseases, is characterized by a progressive reduction in muscle tone and force of the proximal limbs. The clinical manifestations and genetic patterns of LGMD are heterogeneous. This study reported on a 10-year-old male patient with LGMD type 2U who experienced muscle weakness in the lower limbs after exercise. Upon admission, the patient's creatine kinase levels were significantly elevated, and hydration and alkalinization therapy were ineffective. Using high-throughput sequencing, muscular dystrophy-related genes were tested in the patient, his parents, and his sister. The patient was found to have a heterozygous deletion of exon 9 of the ISPD gene and a heterozygous missense mutation c.1231C>T (p.Leu411Phe). The patient's father carried the heterozygous missense mutation c.1231C>T (p.Leu411Phe) of the ISPD gene, while his mother and sister carried a heterozygous deletion of exon 9 of the ISPD gene. These mutations have not been reported in existing databases or literature. Conservation and protein structure prediction analyses of the mutation sites indicated that they are highly conserved and located in the C-terminal domain of the ISPD protein, which may affect protein function. Based on the above results and relevant clinical data, the patient was definitively diagnosed with LGMD type 2U. This study enriched the spectrum of ISPD gene mutations by summarizing the patient's clinical characteristics and analyzing new ISPD gene variations. This can aid in the early diagnosis and genetic counseling of the disease.