Exome sequencing of child-parent trios with bladder exstrophy: Findings in 26 children.
Exome sequencing of child-parent trios with bladder exstrophy: Findings in 26 children.
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患有膀胱外翻的亲子三人组的外显子组测序：26 名儿童的研究结果。
DOI：
10.1002/ajmg.a.62439
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
University of Washington Center for Mendelian Genomics, NISC Comparative Sequencing Program and the National Birth Defects Prevention Study
中科院分区：
文献类型：
--
作者：
Pitsava G;Feldkamp ML;Pankratz N;Lane J;Kay DM;Conway KM;Shaw GM;Reefhuis J;Jenkins MM;Almli LM;Olshan AF;Pangilinan F;Brody LC;Sicko RJ;Hobbs CA;Bamshad M;McGoldrick D;Nickerson DA;Finnell RH;Mullikin J;Romitti PA;Mills JL;University of Washington Center for Mendelian Genomics, NISC Comparative Sequencing Program and the National Birth Defects Prevention Study
膀胱外翻(BE)是一种罕见的下腹中线缺陷，伴有膀胱和部分尿路外露。BE的病因尚不清楚，但被认为受到遗传变异的影响，最近的研究表明，罕见的变异可能起到了作用。因此，我们对26个孩子/母亲/父亲三人组进行了配对末端外显子组测序。三名儿童在TSPAN4中有罕见的遗传变异(等位基因频率≤在几个公共数据库中为0.0001)，一个是功能丧失变异，两个是错义变异。两名儿童在TUBE1中出现了功能丧失的变异。有四个孩子在WNT3、CRKL、Myh9或LZTR1基因上有罕见的错义或无义变异(每个孩子一个)，这些基因以前与BE有关。我们在13名儿童中检测到17个新的错义变异，在3个儿童(每个儿童一个)中检测到3个新的功能丧失变异(AKR1C2，Prrx1，PPM1D)。我们还在PLCH2和CLEC4M中检测到罕见的复合杂合性功能丧失变种，在应用常染色体隐性遗传模式(三个基因)和X连锁隐性遗传模式(13个基因)的其他基因中检测到罕见的遗传性错义或功能丧失变种。已发现的两个基因的变异可能涉及细胞迁移(TUBE1)和黏附(TSPAN4)过程的中断，这是BE的机制，并为罕见的变异在这种缺陷的发展中提供了额外的证据。
Bladder exstrophy (BE) is a rare, lower ventral midline defect with the bladder and part of the urethra exposed. The etiology of BE is unknown but thought to be influenced by genetic variation with more recent studies suggesting a role for rare variants. As such, we conducted paired-end exome sequencing in 26 child/mother/father trios. Three children had rare (allele frequency ≤0.0001 in several public databases) inherited variants in TSPAN4, one with a loss-of-function variant and two with missense variants. Two children had loss-of-function variants in TUBE1. Four children had rare missense or nonsense variants (one per child) in WNT3, CRKL, MYH9, or LZTR1, genes previously associated with BE. We detected 17 de novo missense variants in 13 children and three de novo loss-of-function variants (AKR1C2, PRRX1, PPM1D) in three children (one per child). We also detected rare compound heterozygous loss-of-function variants in PLCH2 and CLEC4M and rare inherited missense or loss-of-function variants in additional genes applying autosomal recessive (three genes) and X-linked recessive inheritance models (13 genes). Variants in two genes identified may implicate disruption in cell migration (TUBE1) and adhesion (TSPAN4) processes, mechanisms proposed for BE, and provide additional evidence for rare variants in the development of this defect.
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影响因子：
3.7
作者：
Derrien T;Estellé J;Marco Sola S;Knowles DG;Raineri E;Guigó R;Ribeca P
通讯作者：
Ribeca P
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
4.5
作者：
Huang N;Lee I;Marcotte EM;Hurles ME
通讯作者：
Hurles ME
影响因子：
--
作者：
BURK, D;SADLER, TW;LANGMAN, J
通讯作者：
LANGMAN, J
影响因子：
5.2
作者：
DUHAMEL, B
通讯作者：
DUHAMEL, B