Yuan Yeqing, Zhou Qiaoli, Wang Chunli, Zhou Wei, Gu Wei, Zheng Bixia
Department of Endocrinology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Front Pediatr. 2023 Jan 11;10:1056141. doi: 10.3389/fped.2022.1056141. eCollection 2022.
A novel autosomal recessive skeletal dysplasia resulting from pathogenic variants in membrane-bound transcription factor peptidase, site 1 () has been recently delineated. To date, only three patients have been reported.
In this study, we reported the clinical and molecular features of a Chinese boy who was diagnosed with spondyloepiphyseal dysplasia. The effects of variants on mRNA splicing were analyzed through transcript analysis and minigene splice assay .
The proband mainly showed short stature, special facial features, cataract, hernias, and serious sleep apnea syndrome. Growth hormone stimulation tests suggested the boy had growth hormone deficiency. Imaging examinations suggested abnormal thoracolumbar vertebrae and severely decreased bone mineral density. Genetic analysis of gene revealed two novel heterozygous variants, a nonsense mutation c.2656C > T (p.Q886*, 167) in exon 20 and a synonymous variant c.774C > T (p.A258=) in exon 6. The transcript analysis exhibited that the synonymous variant c.774C > T caused exon 6 skipping. The minigene splice assay confirmed the alteration of mRNA splicing and the exon skipping was partially restored by an antisense oligonucleotide (ASO) treatment.
Notably, we report a Chinese rare case of spondyloepiphyseal dysplasia and validate its pathogenic synonymous variant in the gene.
最近已明确一种由膜结合转录因子肽酶1（）的致病变异导致的新型常染色体隐性遗传性骨骼发育不良。迄今为止，仅报道了3例患者。
在本研究中，我们报告了一名被诊断为脊椎骨骺发育不良的中国男孩的临床和分子特征。通过转录分析和小基因剪接试验分析了变异对mRNA剪接的影响。
先证者主要表现为身材矮小、特殊面容、白内障、疝气和严重的睡眠呼吸暂停综合征。生长激素刺激试验表明该男孩存在生长激素缺乏。影像学检查提示胸腰椎异常且骨密度严重降低。对基因的遗传分析发现了两个新的杂合变异，一个是外显子20中的无义突变c.2656C>T（p.Q886*，167），另一个是外显子6中的同义变异c.774C>T（p.A258=）。转录分析显示同义变异c.774C>T导致外显子6跳跃。小基因剪接试验证实了mRNA剪接的改变，并且反义寡核苷酸（ASO）处理部分恢复了外显子跳跃。
值得注意的是，我们报告了一例中国脊椎骨骺发育不良的罕见病例，并验证了该基因中的致病性同义变异。
