A novel variant in NPR2: C.2291T > C (p.Leu764Pro) identified in a patient with acromesomelic dysplasia Maroteaux type

在一名患有肢端中段发育不良(Maroteaux型)的患者中发现了一种新的NPR2变异:C.2291T>C(p.Leu764Pro)。

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Abstract

BACKGROUND: Acromesomelic dysplasia Maroteaux type (AMDM) is a rare autosomal recessive skeletal dysplasia with an estimated prevalence of 1:1,000,000. It is characterized by extreme shortening of the forelimbs and disproportionate short stature. CASE PRESENTATION: Here we present the clinical and genetic features of an 8-year-8-month-old boy exhibiting idiopathic short stature and abnormal changes of the appendicular skeleton and axial skeleton, consistent with the established phenotypic spectrum of AMDM. Using diagnostic exome sequencing, we identified two variants in NPR2: a known pathogenic nonsense variant, C.2965 C > T (p.Arg989*), and a missense variant of unknown significance, C.2291T > C (p.Leu764Pro), which has never been reported before. Sanger sequencing confirmed that the variants were inherited from his phenotypically normal parents. The proband is compound heterozygous, while both parents are heterozygous carriers, indicating an autosomal recessive pattern of inheritance. CONCLUSION: This study enriches the pathogenic gene mutation spectrum of NPR2 in patients with AMDM and further emphasizes the application of molecular genetic detection in the diagnosis of rare skeletal abnormalities.

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