Multilocus disease-causing genomic variations for Mendelian disorders: role of systematic phenotyping and implications on genetic counselling.
Multilocus disease-causing genomic variations for Mendelian disorders: role of systematic phenotyping and implications on genetic counselling.
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DOI：
10.1038/s41431-021-00933-7
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Shukla A
中科院分区：
文献类型：
--
作者：
Narayanan DL;Udyawar D;Kaur P;Sharma S;Suresh N;Nampoothiri S;do Rosario MC;Somashekar PH;Rao LP;Kausthubham N;Majethia P;Pande S;Ramesh Bhat Y;Shrikiran A;Bielas S;Girisha KM;Shukla A
多位点致病基因组变异（MGV）和多重遗传诊断（MGD）越来越多地在患有孟德尔疾病的个人和家庭中得到认可。这可以主要归因于基因组测试用于评估这些疾病的广泛使用。我们进行了一项回顾性研究的家庭评估，在过去6年中，在我们的中心，以确定家庭与MGV和MGD。在14个家庭中观察到MGV。我们观察到五种不同的结果：（i）MGV个体呈现为混合表型（ii）MGV个体呈现不同表型（iii）MGV个体具有年龄依赖性突变（iv）MGV个体具有一种表型被另一种更主要的表型掩盖（v）MGV家族中不同个体的两种不同表型。其中8例（8/14，57.1%）有血缘关系。13个家庭有两个孟德尔疾病和一个有三个孟德尔疾病。这些家庭中一种或多种疾病复发的风险范围为25%至75%。我们的研究结果强调了临床遗传学家在系统表型分析中的作用的重要性，遗传咨询和风险估计在MGV和MGD家族中的挑战，特别是在高度近交的人群中。
Multilocus disease-causing genomic variations (MGVs) and multiple genetic diagnoses (MGDs) are increasingly being recognised in individuals and families with Mendelian disorders. This can be mainly attributed to the widespread use of genomic tests for the evaluation of these disorders. We conducted a retrospective study of families evaluated over the last 6 years at our centre to identify families with MGVs and MGDs. MGVs were observed in fourteen families. We observed five different consequences: (i) individuals with MGVs presenting as blended phenotypes (ii) individuals with MGVs presenting with distinct phenotypes (iii) individuals with MGVs with age-dependent penetrance (iv) individuals with MGVs with one phenotype obscured by another more predominant phenotype (v) two distinct phenotypes in different individuals in families with MGVs. Consanguinity was present in eight (8/14, 57.1%) of them. Thirteen families had two Mendelian disorders and one had three Mendelian disorders. The risk of recurrence of one or more conditions in these families ranged from 25% to 75%. Our findings underline the importance of the role of a clinical geneticist in systematic phenotyping, challenges in genetic counselling and risk estimation in families with MGVs and MGDs, especially in highly inbred populations.
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影响因子：
2
作者：
Somashekar, Puneeth H.;Upadhyai, Priyanka;Shukla, Anju
通讯作者：
Shukla, Anju
影响因子：
5.3
作者：
Yavarna, Tarunashree;Al-Dewik, Nader;Ben-Omran, Tawfeg
通讯作者：
Ben-Omran, Tawfeg
影响因子：
3.9
作者：
Hennekam, Raoul C. M.;Biesecker, Leslie G.
通讯作者：
Biesecker, Leslie G.
DOI：
10.1056/nejmoa1516767
发表时间：
2017-01-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Posey JE;Harel T;Liu P;Rosenfeld JA;James RA;Coban Akdemir ZH;Walkiewicz M;Bi W;Xiao R;Ding Y;Xia F;Beaudet AL;Muzny DM;Gibbs RA;Boerwinkle E;Eng CM;Sutton VR;Shaw CA;Plon SE;Yang Y;Lupski JR
通讯作者：
Lupski JR
影响因子：
3.5
作者：
Balci, T. B.;Hartley, T.;Boycott, K. M.
通讯作者：
Boycott, K. M.