PDF(Pubmed)
Abstract：
UNASSIGNED: A novel autosomal recessive skeletal dysplasia resulting from pathogenic variants in membrane-bound transcription factor peptidase, site 1 (MBTPS1) has been recently delineated. To date, only three patients have been reported.
UNASSIGNED: 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 in vivo and minigene splice assay in vitro.
UNASSIGNED: 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 MBTPS1 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 in vivo exhibited that the synonymous variant c.774C > T caused exon 6 skipping. The minigene splice assay in vitro confirmed the alteration of MBTPS1 mRNA splicing and the exon skipping was partially restored by an antisense oligonucleotide (ASO) treatment.
UNASSIGNED: Notably, we report a Chinese rare case of spondyloepiphyseal dysplasia and validate its pathogenic synonymous variant in the MBTPS1 gene.
UNASSIGNED: 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 in vivo and minigene splice assay in vitro.
UNASSIGNED: 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 MBTPS1 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 in vivo exhibited that the synonymous variant c.774C > T caused exon 6 skipping. The minigene splice assay in vitro confirmed the alteration of MBTPS1 mRNA splicing and the exon skipping was partially restored by an antisense oligonucleotide (ASO) treatment.
UNASSIGNED: Notably, we report a Chinese rare case of spondyloepiphyseal dysplasia and validate its pathogenic synonymous variant in the MBTPS1 gene.
摘要：
未经证实：一种由膜结合转录因子肽酶致病变异导致的新型常染色体隐性遗传骨骼发育不良，站点1（MBTPS1）最近已划定。迄今为止,仅报告了三名患者。
未经批准：在这项研究中，我们报道了一名中国男孩的临床和分子特征，该男孩被诊断为脊柱骨发育不良。通过体内转录分析和体外小基因剪接测定分析变体对mRNA剪接的影响。
未经授权：先证者主要表现为身材矮小，特殊的面部特征，白内障,疝气,和严重的睡眠呼吸暂停综合症。生长激素刺激测试表明该男孩患有生长激素缺乏症。影像学检查提示胸腰椎异常，骨密度严重下降。MBTPS1基因的遗传分析揭示了两个新的杂合变异，无意义突变c.2656C>T（p。Q886*,167）在外显子20和同义变体c.774C>T（p。A258=)在外显子6。体内转录物分析显示同义变体c.774C>T引起外显子6跳跃。体外小基因剪接测定证实了MBTPS1mRNA剪接的改变，并且通过反义寡核苷酸（ASO）处理部分恢复了外显子跳跃。
未经评估：特别是，我们报告了一例中国罕见的脊柱骨骨发育不良病例，并验证了其在MBTPS1基因中的致病同义变异。
未经批准：在这项研究中，我们报道了一名中国男孩的临床和分子特征，该男孩被诊断为脊柱骨发育不良。通过体内转录分析和体外小基因剪接测定分析变体对mRNA剪接的影响。
未经授权：先证者主要表现为身材矮小，特殊的面部特征，白内障,疝气,和严重的睡眠呼吸暂停综合症。生长激素刺激测试表明该男孩患有生长激素缺乏症。影像学检查提示胸腰椎异常，骨密度严重下降。MBTPS1基因的遗传分析揭示了两个新的杂合变异，无意义突变c.2656C>T（p。Q886*,167）在外显子20和同义变体c.774C>T（p。A258=)在外显子6。体内转录物分析显示同义变体c.774C>T引起外显子6跳跃。体外小基因剪接测定证实了MBTPS1mRNA剪接的改变，并且通过反义寡核苷酸（ASO）处理部分恢复了外显子跳跃。
未经评估：特别是，我们报告了一例中国罕见的脊柱骨骨发育不良病例，并验证了其在MBTPS1基因中的致病同义变异。
