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.肢带型肌营养不良症(limb-girdle muscular dystrophy，LGMD)是一组罕见的非先天性遗传性肌肉疾病，主要表现为四肢近端肌张力及肌力进行性减退，其临床表现及遗传模式具有异质性。本研究报道了1例肢带型肌营养不良症2U型10岁男性患者，运动后出现双下肢肌肉无力，入院查肌酸激酶明显升高，经水化碱化治疗后无效。利用高通量测序方法对患者及其父母、妹妹进行肌营养不良相关基因检测，该患者存在ISPD基因外显子9杂合缺失以及c.1231C>T(p.Leu411Phe)的杂合错义变异，其父亲携带ISPD基因c.1231C>T(p.Leu411Phe)的杂合错义变异，母亲及妹妹携带ISPD基因外显子9杂合缺失，上述变异在现有的数据库及文献中均未见报道。对变异位点的保守性分析和蛋白结构预测分析表明，上述位点保守性高，且均位于ISPD蛋白C端结构域，可能对蛋白功能产生影响。综合以上结果并结合相关临床资料，可明确诊断该患者为肢带型肌营养不良症2U型。本文通过总结该患者临床特点及对ISPD基因新变异进行分析，丰富了ISPD基因变异谱，有助于该病早期诊断及遗传咨询。.