A recurrent 8 bp frameshifting indel in FOXF1 defines a novel mutation hotspot associated with alveolar capillary dysplasia with misalignment of pulmonary veins.
A recurrent 8 bp frameshifting indel in FOXF1 defines a novel mutation hotspot associated with alveolar capillary dysplasia with misalignment of pulmonary veins.
复制标题
FOXF1 中反复出现的 8 bp 移码插入缺失定义了与肺泡毛细血管发育不良伴肺静脉错位相关的新突变热点。
DOI：
10.1002/ajmg.a.61338
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Stankiewicz,Paweł
中科院分区：
文献类型：
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作者：
Karolak,JustynaA;Bacolla,Albino;Liu,Qian;Lantz,PatrickE;Petty,John;Trapane,Pamela;Panzer,Karin;Totapally,BalagangadharR;Niu,Zhiyv;Xiao,Rui;Xie,NinaG;Wu,LuciaR;Szafranski,Przemyslaw;Zhang,DavidY;Stankiewicz,Paweł
肺泡毛细血管发育不良伴肺静脉错位（ACDMPV）是一种罕见的致死性肺发育疾病。受影响的婴儿表现为严重的呼吸窘迫和难治性肺动脉高压，并在生命的第一个月内均匀死亡。在绝大多数ACDMPV患者中发现了涉及foxf1和/或其上游肺特异性增强子16q24.1的杂合点突变或拷贝数变异缺失。我们之前已经描述了两个不相关的家族，它们在ofoxf1的外显子1中有一个新的致病移码变体c.691_698del （p.Ala231Argfs*61）。在这里，我们提出了第三个不相关的ACDMPV家族，具有相同的从头变异体，并提出在~ 4kb CpG岛inFOXF1exon 1内的8个连续核苷酸GCGGCGGC的直接串连重复是ACDMPV的一个新的突变热点病因。
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal lung developmental disease. Affected infants manifest with severe respiratory distress and refractory pulmonary hypertension and uniformly die in the first month of life. Heterozygous point mutations or copy‐number variant deletions involvingFOXF1and/or its upstream lung‐specific enhancer on 16q24.1 have been identified in the vast majority of ACDMPV patients. We have previously described two unrelated families with a de novo pathogenic frameshift variant c.691_698del (p.Ala231Argfs*61) in the exon 1 ofFOXF1. Here, we present a third unrelated ACDMPV family with the same de novo variant and propose that a direct tandem repeat of eight consecutive nucleotides GCGGCGGC within the ~4 kb CpG island inFOXF1exon 1 is a novel mutation hotspot causative for ACDMPV.