一种新的双等位基因功能丧失变异导致DAND5异位综合征。

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2022-12-01 DOI:10.1101/mcs.a006248
Mythily Ganapathi, Christie M Buchovecky, Fernando Cristo, Priyanka Ahimaz, Carrie Ruzal-Shapiro, Karen Wou, José M Inácio, Alejandro Iglesias, José A Belo, Vaidehi Jobanputra
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引用次数: 0

摘要

虽然已知超过50种基因的致病变异可导致异源性,但大多数异源性病例无法获得分子诊断。结抑制剂DAND5的杂合错义变体在早期发育中起作用,建立了左右模式,这与杂性有关。最近,报道了首例DAND5双等位基因功能丧失(LoF)变异在异交个体中的发生。在这里,我们描述了第二个不相关的个体,具有异位综合征和DAND5 (NM_152654.2:c)的纯合移码变异。197年del [p.Leu66ArgfsTer22])。通过体外实验,我们证明与野生型表达结构相比,DAND5 c.197del变体无法抑制节点信号传导。这项工作加强了DAND5双等位LoF变异引起常染色体隐性异位综合征的遗传和功能证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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A novel biallelic loss-of-function variant in DAND5 causes heterotaxy syndrome.

The majority of heterotaxy cases do not obtain a molecular diagnosis, although pathogenic variants in more than 50 genes are known to cause heterotaxy. A heterozygous missense variant in DAND5, a nodal inhibitor, which functions in early development for establishment of right-left patterning, has been implicated in heterotaxy. Recently, the first case was reported of a DAND5 biallelic loss-of-function (LoF) variant in an individual with heterotaxy. Here, we describe a second unrelated individual with heterotaxy syndrome and a homozygous frameshift variant in DAND5 (NM_152654.2:c.197del [p.Leu66ArgfsTer22]). Using an in vitro assay, we demonstrate that the DAND5 c.197del variant is unable to inhibit nodal signaling when compared with the wild-type expression construct. This work strengthens the genetic and functional evidence for biallelic LoF variants in DAND5 causing an autosomal recessive heterotaxy syndrome.

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来源期刊
Cold Spring Harbor Molecular Case Studies
Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.20
自引率
0.00%
发文量
54
期刊介绍: Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.
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