A case report of SPONASTRIME dysplasia with novel TONSL mutation: genetic analysis, clinical manifestations, and the effect of growth hormone treatment

一例伴有新型TONSL突变的SPONASTRIME发育不良病例报告:基因分析、临床表现及生长激素治疗效果

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Abstract

SPONASTRIME dysplasia is a rare genetic disorder characterized by short stature, facial abnormalities, vertebral issues, and bone striations, caused by recessive mutations in the TONSL gene. We reported a 6-year-old boy with characteristic clinical features of SPONASTRIME dysplasia, accompanied by neutropenia. Genetic analysis revealed biallelic variants in TONSL: mother-inherited c.1289del (p.Gln430ArgfsTer13) and father-inherited c.1961G > C (p.Arg654Pro), both of which were previously unreported. We predicted the c.1289del (p.Gln430ArgfsTer13) variant as likely pathogenic in silico analysis, while the c.1961G > C (p.Arg654Pro) variant as uncertain pathogenicity in silico analysis, and the pathogenicity was confirmed by functional studies in transfected HEK 293 T cells. Six-month growth hormone therapy was administered to the patient after confirmed diagnosis, with limited improvement. These findings have important implications for the diagnosis and treatment of the disease.

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