Homozygous missense variant in BMPR1A resulting in BMPR signaling disruption and syndromic features.
Homozygous missense variant in BMPR1A resulting in BMPR signaling disruption and syndromic features.
复制标题
BMPR1A 中的纯合错义变异导致 BMPR 信号传导破坏和综合征特征。
DOI：
10.1002/mgg3.969
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发表时间：
2019
影响因子：
2
通讯作者：
Dauber,Andrew
中科院分区：
文献类型：
--
作者：
Russell,BiancaE;Rigueur,Diana;Weaver,KathrynN;Sund,Kristen;Basil,JanetS;Hufnagel,RobertB;Prows,CynthiaA;Oestreich,Alan;Al-Gazali,Lihadh;Hopkin,RobertJ;Saal,HowardM;Lyons,Karen;Dauber,Andrew
骨形态发生蛋白（BMP）通路在骨、软骨和心脏组织形成中起着重要作用。骨形态发生蛋白受体1a型（BMPR1A）的截断、杂合变异体和缺失与常染色体显性青少年性息肉病有关。杂合缺失也与心脏和轻微的骨骼异常有关。房室间隔缺损人群中罕见的缺失bmpr1变异丰富。方法我们报告了一例bmpr1纯合子错义变异导致骨骼异常、生长衰竭、大面积房间隔缺损、严重声门下狭窄、喉软化、面部畸形和发育迟缓的患者。结果该变异的功能分析显示，携带突变受体的细胞的软骨细胞死亡增加，磷酸化的R - Smads1/5/8增加，p38磷酸化降低介导的Sox9表达缺失。结论BMPR1A纯合子错义变异可引起不同的临床表型。
BackgroundThe bone morphogenetic protein (BMP) pathway is known to play an imperative role in bone, cartilage, and cardiac tissue formation. Truncating, heterozygous variants, and deletions of one of the essential receptors in this pathway, Bone Morphogenetic Protein Receptor Type1A (BMPR1A), have been associated with autosomal dominant juvenile polyposis. Heterozygous deletions have also been associated with cardiac and minor skeletal anomalies. Populations with atrioventricular septal defects are enriched for rare missenseBMPR1Avariants.MethodsWe report on a patient with a homozygous missense variant inBMPR1Acausing skeletal abnormalities, growth failure a large atrial septal defect, severe subglottic stenosis, laryngomalacia, facial dysmorphisms, and developmental delays.ResultsFunctional analysis of this variant shows increased chondrocyte death for cells with the mutated receptor, increased phosphorylated R‐Smads1/5/8, and loss of Sox9 expression mediated by decreased phosphorylation of p38.ConclusionThis homozygous missense variant in BMPR1A appears to cause a distinct clinical phenotype.