家族传说、意义不明的变异体和 CADASIL。

IF 2.8 3区 医学 Q2 GENETICS & HEREDITY
Rhys Duarte, Liesbeth Vossaert, Sandra A Darilek, Chelsi Rose, Evan Schauer, Christian Parobek, Emily Bland, Keren Machol, Elizabeth Mizerik, Chaya N Murali
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引用次数: 0

摘要

一名婴儿病危。在医疗团队稳定了他的病情后,就开始寻找他患病的原因。遗传学会诊小组认为,他的问题不太可能是由遗传原因引起的,但他的极端、令人困惑的表现足以证明进行三组外显子测序是正确的。测序结果显示,NOTCH3 存在一个意想不到的父方遗传的意义不确定变体 (VUS),新的问题随之而来。该婴儿的主要症状和描述性诊断(包括吐血、鼻衄和胃溃疡)当然不符合 CADASIL 的模式。然而,仔细观察他的家族病史会发现一些诱人的线索:父亲和祖父有癫痫发作,祖父在中年时有不明原因的情绪紊乱。结合从家族病史和医学文献中收集到的细节,临床遗传学和实验室遗传学团队通力合作,将 VUS 重新归类为可能致病的疾病,并提供了一个新的统一诊断,以解释该家族的许多传说。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Family Lore, a Variant of Uncertain Significance, and CADASIL.

An infant presents in extremis. After the medical team stabilizes him, the race is on to figure out why he got so sick in the first place. The consulting genetics team thinks that it is unlikely his problems are due to a genetic cause, but his extreme, confounding presentation is enough to justify trio exome sequencing. When the results reveal an unexpected, paternally inherited variant of uncertain significance (VUS) in NOTCH3, fresh questions arise. The infant's presenting symptoms and descriptive diagnoses, including hematemesis, epistaxis, and gastric ulcers, certainly do not fit the mold of CADASIL. However, closer inspection of his family history yields tantalizing clues: a father and paternal grandfather with seizures, and a paternal grandfather with unexplained mood disturbances in middle age. Combining details gleaned from the family history and medical literature, the clinical genetics and laboratory genetics team collaborated, reclassified the VUS as likely pathogenic, and offered a new unifying diagnosis to explain much of the family's lore.

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来源期刊
CiteScore
7.00
自引率
0.00%
发文量
42
审稿时长
>12 weeks
期刊介绍: Seminars in Medical Genetics, Part C of the American Journal of Medical Genetics (AJMG) , serves as both an educational resource and review forum, providing critical, in-depth retrospectives for students, practitioners, and associated professionals working in fields of human and medical genetics. Each issue is guest edited by a researcher in a featured area of genetics, offering a collection of thematic reviews from specialists around the world. Seminars in Medical Genetics publishes four times per year.
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