Urinary Tract Effects of HPSE2 Mutations
Urinary Tract Effects of HPSE2 Mutations
复制标题
DOI：
10.1681/asn.2013090961
复制
发表时间：
2015-04-01
影响因子：
13.6
通讯作者：
Woolf, Adrian S.
中科院分区：
文献类型：
--
作者：
Stuart, Helen M.;Roberts, Neil A.;Woolf, Adrian S.
泌尿面综合征是一种常染色体隐性遗传的先天性疾病，以面部表情扭曲和膀胱排空不全为特征。HPSE2突变，编码乙酰肝素酶2，乙酰肝素酶1抑制剂，发生在UFS，但知识的HPSE2突变谱是有限的。在这里，七个UFS激酶HPSE2突变，包括一个缺失的天冬酰胺254，这表明这种氨基酸的作用，这是保守的脊椎动物直系同源物。在23个非神经源性神经源性膀胱先证者和439个非综合征性膀胱输尿管反流家族中，只有一个家族携带假定的致病性HPSE 2变异体。纯合Hpse 2突变小鼠膀胱比野生型器官更常含有尿液，这与人类UFS的表型相似。盆神经节神经细胞体含有乙酰肝素酶1、乙酰肝素酶2和富含亮氨酸的重复序列和免疫球蛋白样结构域2（LRIG2），其在某些UFS家族中发生突变。总之，乙酰肝素酶2是一种与膀胱排空有关的自主神经蛋白，但HPSE 2变体在类似UFS的泌尿系统疾病中并不常见。
Urofacial syndrome (UFS) is an autosomal recessive congenital disease featuring grimacing and incomplete bladder emptying. Mutations of HPSE2, encoding heparanase 2, a heparanase 1 inhibitor, occur in UFS, but knowledge about the HPSE2 mutation spectrum is limited. Here, seven UFS kindreds with HPSE2 mutations are presented, including one with deleted asparagine 254, suggesting a role for this amino acid, which is conserved in vertebrate orthologs. HPSE2 mutations were absent in 23 non-neurogenic neurogenic bladder probands and, of 439 families with nonsyndromic vesicoureteric reflux, only one carried a putative pathogenic HPSE2 variant. Homozygous Hpse2 mutant mouse bladders contained urine more often than did wild-type organs, phenocopying human UFS. Pelvic ganglia neural cell bodies contained heparanase 1, heparanase 2, and leucine-rich repeats and immunoglobulin-like domains-2 (LRIG2), which is mutated in certain UFS families. In conclusion, heparanase 2 is an autonomic neural protein implicated in bladder emptying, but HPSE2 variants are uncommon in urinary diseases resembling UFS.