LRIG2 Mutations Cause Urofacial Syndrome
LRIG2 Mutations Cause Urofacial Syndrome
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DOI：
10.1016/j.ajhg.2012.12.002
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发表时间：
2013-02-07
影响因子：
9.8
通讯作者：
Newman, William G.
中科院分区：
文献类型：
--
作者：
Stuart, Helen M.;Roberts, Neil A.;Newman, William G.
Urofacial syndrome（UFS）（或Ochoa syndrome）是一种常染色体隐性遗传疾病，其特征是先天性膀胱功能障碍，与肾衰竭的显著风险相关，以及微笑、大笑和哭泣时的异常面部表情。我们报告说，一个子集的UFS受影响的个人有双等位基因突变LRIG 2，编码富含亮氨酸的重复序列和免疫球蛋白样结构域2，一种蛋白质参与神经细胞信号传导和肿瘤发生。重要的是，我们已经证明LRIG 2的罕见变异可能与非综合征性膀胱疾病相关。我们以前已经表明，UFS也是由HPSE 2（编码乙酰肝素酶-2）突变引起的。LRIG 2和乙酰肝素酶-2在人胎儿膀胱内肌束之间生长的神经束中被免疫检测到，这直接涉及下尿路神经发育中的两种分子。
Urofacial syndrome (UFS) (or Ochoa syndrome) is an autosomal-recessive disease characterized by congenital urinary bladder dysfunction, associated with a significant risk of kidney failure, and an abnormal facial expression upon smiling, laughing, and crying. We report that a subset of UFS-affected individuals have biallelic mutations in LRIG2, encoding leucine-rich repeats and immunoglobulin-like domains 2, a protein implicated in neural cell signaling and tumorigenesis. Importantly, we have demonstrated that rare variants in LRIG2 might be relevant to nonsyndromic bladder disease. We have previously shown that UFS is also caused by mutations in HPSE2, encoding heparanase-2. LRIG2 and heparanase-2 were immunodetected in nerve fascicles growing between muscle bundles within the human fetal bladder, directly implicating both molecules in neural development in the lower urinary tract.