Early B-cell Factor 3-Related Genetic Disease Can Mimic Urofacial Syndrome.
Early B-cell Factor 3-Related Genetic Disease Can Mimic Urofacial Syndrome.
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DOI：
10.1016/j.ekir.2020.07.001
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发表时间：
2020-10
影响因子：
6
通讯作者：
Newman WG
中科院分区：
文献类型：
--
作者：
Harkness JR;Beaman GM;Teik KW;Sidhu S;Sayer JA;Cordell HJ;Thomas HB;Wood K;Stuart HM;Woolf AS;Newman WG
几十年前，Bernardo Ochoa描述了一种罕见但具有潜在破坏性的遗传性疾病，现在称为urofacial或Ochoa综合征（UFS）。2 UFS有两个特点。首先，所谓的“非神经性神经性”协同失调膀胱，其中功能性膀胱流出道梗阻引起不完全排尿、膀胱输尿管反流（VUR）、上行性尿脓毒症、肾盂肾炎和肾衰竭。第二种是一种鬼脸，微笑时嘴角向下，使脸看起来像在哭。据报道，大约三分之二的病例会出现严重便秘。1 Ochoa的1个队列来自哥伦比亚，但UFS随后在全球范围内报告，病例总数至少为150例。2 UFS是一种常染色体隐性遗传疾病，大多数病例是由以下2种基因中的任一种的双等位基因致病性变体引起的：HPSE 2（Mendelian Inheritance in Man（MIM）613469）3、4、5编码乙酰肝素酶-2，其抑制经典乙酰肝素酶或LRIG 2的酶活性（MIM 615112）6编码富含亮氨酸的重复序列和Ig样结构域，一种可调节生长因子信号传导的蛋白质。乙酰肝素酶2和LRIG 2蛋白存在于骨盆神经节和从这些神经节发出的膀胱自主神经中，5、6、7并且膀胱神经的模式在携带Hpse 2或Lrig 2中的双等位基因变体的小鼠中异常。5，6，7因此，UFS的特征是影响膀胱的周围神经病变，而鬼脸的原因需要进一步研究。少数明显临床诊断为UFS的人不携带HPSE 2或LRIG 2变异。5，6，7本报告提请注意一种不同的遗传综合征，它可以模仿UFS并与肾衰竭相关。我们描述了一个这样的个人与杂合错义预测致病性变异早期B细胞因子3（EBF 3），一个基因编码的转录因子，并与张力减退，共济失调，发育迟缓综合征（HADDS; MIM 617330）。8，9，S1我们在英国一个家族性原发性非综合征性VUR S2队列中寻找EBF 3的变异，并回顾了HADDS的已发表文献，以确定其他此类个体是否患有肾脏疾病。
Several decades ago, Bernardo Ochoa 1 described a rare but potentially devastating inherited disease that is now called urofacial, or Ochoa, syndrome (UFS). 2 UFS is characterized by 2 features. First, a so-called “non-neurogenic neurogenic” dyssynergic bladder in which functional bladder outflow obstruction causes incomplete voiding, vesicoureteric reflux (VUR), ascending urosepsis, pyelonephritis, and renal failure. Second, a grimace where the corners of the mouth become downturned on smiling, so that the face appears to be crying. Severe constipation is reported in approximately two-thirds of cases. 1 Ochoa’s 1 cohort was from Colombia, but UFS has subsequently been reported worldwide and cases totaled at least 150. 2 UFS is an autosomal recessive disorder and most cases are caused by biallelic pathogenic variants in either of 2 genes: HPSE2 (Mendelian Inheritance in Man (MIM) 613469) 3, 4, 5 encoding heparanase-2, which inhibits the enzymatic activity of classical heparanase, or LRIG2 (MIM 615112) 6 encoding leucine-rich repeats and Ig-like domains, a protein that may modulate growth factor signaling. Heparanase 2 and LRIG2 proteins are present in pelvic ganglia and in bladder autonomic nerves emanating from these ganglia, 5, 6, 7 and the patterns of bladder nerves are abnormal in mice carrying biallelic variants in either Hpse2 or Lrig2. 5, 6, 7 Thus, UFS features a peripheral neuropathy affecting the bladder, whereas the cause of the grimace requires further study.A minority of people with an apparent clinical diagnosis of UFS do not carry variants in HPSE2 or LRIG2. 5, 6, 7 The current report draws attention to a different genetic syndrome, which can mimic UFS and be associated with renal failure. We describe one such individual with a heterozygous missense predicted pathogenic variant in early B-cell factor 3 (EBF3), a gene encoding a transcription factor and associated with hypotonia, ataxia, and developmental delay syndrome (HADDS; MIM 617330). 8, 9, S1 We proceeded to seek variants in EBF3 in a UK cohort with familial primary nonsyndromic VUR S2 and reviewed the published literature of HADDS to determine whether other such individuals had renal tract disease.
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影响因子：
1.8
作者：
Tanaka AJ;Cho MT;Willaert R;Retterer K;Zarate YA;Bosanko K;Stefans V;Oishi K;Williamson A;Wilson GN;Basinger A;Barbaro-Dieber T;Ortega L;Sorrentino S;Gabriel MK;Anderson IJ;Sacoto MJG;Schnur RE;Chung WK
通讯作者：
Chung WK
影响因子：
13.6
作者：
Stuart, Helen M.;Roberts, Neil A.;Woolf, Adrian S.
通讯作者：
Woolf, Adrian S.
影响因子：
9.8
作者：
Stuart, Helen M.;Roberts, Neil A.;Newman, William G.
通讯作者：
Newman, William G.
影响因子：
9.8
作者：
Harms FL;Girisha KM;Hardigan AA;Kortüm F;Shukla A;Alawi M;Dalal A;Brady L;Tarnopolsky M;Bird LM;Ceulemans S;Bebin M;Bowling KM;Hiatt SM;Lose EJ;Primiano M;Chung WK;Juusola J;Akdemir ZC;Bainbridge M;Charng WL;Drummond-Borg M;Eldomery MK;El-Hattab AW;Saleh MAM;Bézieau S;Cogné B;Isidor B;Küry S;Lupski JR;Myers RM;Cooper GM;Kutsche K
通讯作者：
Kutsche K
影响因子：
9.8
作者：
Pang, Junfeng;Zhang, Shu;Wang, Cong-Yi
通讯作者：
Wang, Cong-Yi