Recessive CHRM5 variant as a potential cause of neurogenic bladder.
Recessive CHRM5 variant as a potential cause of neurogenic bladder.
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隐性 CHRM5 变异是神经源性膀胱的潜在原因。
DOI：
10.1002/ajmg.a.63241
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Eid,L
中科院分区：
文献类型：
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作者：
Schneider,Sophia;Schierbaum,Luca;Burger,WesselAC;Seltzsam,Steve;Wang,Chunyan;Zheng,Bixia;Wu,Chen-HanWilfred;Nakayama,Makiko;Connaughton,DervlaM;Mann,Nina;Shalaby,MohamedA;Kari,JameelaA;ElDesoky,Sherif;Tasic,Velibor;Eid,L
神经源性膀胱是由调节膀胱舒张和收缩的神经元通路破坏引起的。在严重的情况下，神经源性膀胱可导致膀胱输尿管反流、输尿管积水和慢性肾脏疾病。这些并发症与肾脏和泌尿道先天性异常（CAKUT）的表现重叠。为了确定神经源性膀胱的新单基因原因，我们对 CAKUT 家族队列应用了外显子组测序 (ES)。通过 ES，我们在患有神经源性膀胱和 CAKUT 继发并发症的患者中鉴定出 CHRM5（胆碱能受体，毒蕈碱，5）中的纯合错义变异 (p.Gln184Arg)。CHRM5 编码七次跨膜 G 蛋白偶联毒蕈碱乙酰胆碱受体。CHRM5 在小鼠和人类膀胱壁中表达，据报道会导致膀胱过度活动在Chrm5基因敲除小鼠中。我们研究了 CHRM5 作为具有 CAKUT 继发性并发症的神经源性膀胱的潜在新候选基因。CHRM5 与胆碱能膀胱神经元受体 CHRNA3 相似，Mann 等人。作为神经源性膀胱的第一个单基因原因发表。然而，功能性体外研究并未揭示出加强候选基因地位的证据。发现具有 CHRM5 变体的其他家族可能有助于进一步评估基因的候选状态。
Neurogenic bladder is caused by disruption of neuronal pathways regulating bladder relaxation and contraction. In severe cases, neurogenic bladder can lead to vesicoureteral reflux, hydroureter, and chronic kidney disease. These complications overlap with manifestations of congenital anomalies of the kidney and urinary tract (CAKUT). To identify novel monogenic causes of neurogenic bladder, we applied exome sequencing (ES) to our cohort of families with CAKUT. By ES, we have identified a homozygous missense variant (p.Gln184Arg) inCHRM5(cholinergic receptor,muscarinic,5) in a patient with neurogenic bladder and secondary complications of CAKUT.CHRM5codes for a seven transmembrane‐spanning G‐protein‐coupled muscarinic acetylcholine receptor.CHRM5is shown to be expressed in murine and human bladder walls and is reported to cause bladder overactivity inChrm5knockout mice. We investigatedCHRM5as a potential novel candidate gene for neurogenic bladder with secondary complications of CAKUT.CHRM5is similar to the cholinergic bladder neuron receptorCHRNA3, which Mann et al. published as the first monogenic cause of neurogenic bladder. However, functional in vitro studies did not reveal evidence to strengthen the status as a candidate gene. Discovering additional families withCHRM5variants could help to further assess the genes' candidate status.