Homozygous WNT9B variants in two families with bilateral renal agenesis/hypoplasia/dysplasia.
Homozygous WNT9B variants in two families with bilateral renal agenesis/hypoplasia/dysplasia.
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两个双侧肾发育不全/发育不全/发育不良家族的纯合 WNT9B 变异。
DOI：
10.1002/ajmg.a.62398
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Sawyer SL
中科院分区：
文献类型：
--
作者：
Lemire G;Zheng B;Ediae GU;Zou R;Bhola PT;Chisholm C;de Nanassy J;Lo B;Wang C;Shril S;El Desoky S;Shalaby M;Kari JA;Wang X;Care4Rare Canada Consortium;Kernohan KD;Boycott KM;Hildebrandt F;Sawyer SL
WNT9B在哺乳动物泌尿生殖系统的发育中起着关键作用。它对中肾和后肾小管的诱导、肾小管形态发生的调控以及肾祖细胞的增殖和分化具有重要作用。据我们所知，WNT9B与人类肾脏缺陷无关；然而，WNT9B - / -小鼠存在肾脏发育不全/发育不全和生殖道异常。我们报告了来自两个不相关的近亲家庭的四个人，他们患有双侧肾发育不全/发育不全/发育不良和WNT9B纯合变异体。家族1先证者有双侧肾囊性发育不良和慢性肾脏疾病。他有两个已故的兄弟姐妹，表现为双侧肾发育不全。WNT9B错义变异（NM_003396.2: c.949G> a /p.(Gly317Arg)）为纯合子。家族2先证者患有肾发育不全/发育不良，慢性肾病，WNT9B无义变异纯合子（NM_003396.2: c.11dupC/p.(Pro5Alafs*52)）。她的两个兄弟姐妹在新生儿期死亡，其中一个被证实是羊水过少。先证者未受影响的兄弟也是WNT9B无义变异的纯合子，表明非外显性。我们提出了一种新的WNT9B与人类肾脏异常的关联。需要进一步的研究来描述WNT9B在人类泌尿生殖系统异常中的作用。
WNT9B plays a key role in the development of the mammalian urogenital system. It is essential for the induction of mesonephric and metanephric tubules, the regulation of renal tubule morphogenesis, and the regulation of renal progenitor cell expansion and differentiation. To our knowledge, WNT9B has not been associated with renal defects in humans; however, WNT9B−/− mice have renal agenesis/hypoplasia and reproductive tract abnormalities. We report four individuals from two unrelated consanguineous families with bilateral renal agenesis/hypoplasia/dysplasia and homozygous variants in WNT9B. The proband from Family 1 has bilateral renal cystic dysplasia and chronic kidney disease. He has two deceased siblings who presented with bilateral renal hypoplasia/agenesis. The three affected family members were homozygous for a missense variant in WNT9B (NM_003396.2: c.949G>A/p.(Gly317Arg)). The proband from Family 2 has renal hypoplasia/dysplasia, chronic kidney disease, and is homozygous for a nonsense variant in WNT9B (NM_003396.2: c.11dupC/p.(Pro5Alafs*52)). Two of her siblings died in the neonatal period, one confirmed to be in the context of oligohydramnios. The proband’s unaffected brother is also homozygous for the nonsense variant in WNT9B, suggesting non-penetrance. We propose a novel association of WNT9B and renal anomalies in humans. Further study is needed to delineate the contribution of WNT9B to genitourinary anomalies in humans.
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影响因子：
11.8
作者：
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通讯作者：
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通讯作者：
Moore, Helen F.