NPHP4 mutation is linked to cerebello-oculo-renal syndrome and male infertility

被引:17
作者
Alazami, A. M. [1 ]
Alshammari, M. J. [1 ,2 ]
Baig, M. [3 ]
Salih, M. A. [2 ]
Hassan, H. H. [4 ,5 ]
Alkuraya, F. S. [1 ,2 ,6 ]
机构
[1] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia
[2] King Saud Univ, King Khalid Univ Hosp, Dept Pediat, Riyadh, Saudi Arabia
[3] King Saud Univ, King Khalid Univ Hosp, Dept Pathol & Lab Med, Riyadh, Saudi Arabia
[4] King Saud Univ, King Khalid Univ Hosp, Dept Radiol, Riyadh, Saudi Arabia
[5] King Saud Univ, Coll Med, Riyadh 11461, Saudi Arabia
[6] Alfaisal Univ, Coll Med, Dept Anat & Cell Biol, Riyadh, Saudi Arabia
关键词
ciliopathy; nephrocystin; nephronophthisis; sperm; JUVENILE NEPHRONOPHTHISIS; NEPHROCYSTIN-4; MORPHOGENESIS; CHILDREN; PROTEIN; ENCODES;
D O I
10.1111/cge.12160
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Nephronophthisis is the most common genetic cause of renal failure in children and young adults. It is genetically heterogeneous and can be seen in isolation or in combination with other ciliopathy phenotypes. Here we report an index case where nephronophthisis is associated with oculomotor apraxia and cerebellar abnormalities, consistent with the clinical diagnosis of cerebello-oculo-renal syndrome. Prompted by a family history of an uncle with early onset end stage renal failure and infertility, we performed semen analysis on the index. This revealed marked reduction in the count of motile sperms as well as multiple abnormalities in the head and tail. Autozygome-guided mutation analysis followed by exome sequencing and segregation analysis revealed a homozygous truncating mutation in NPHP4, indicating that mutations of this gene can on rare occasions cause cerebello-oculo-renal syndrome. Our finding of severe male infertility in a family with NPHP4 truncation is strongly supported by the mouse model and, to our knowledge, is the first reported male infertility phenotype in association with NPHP4 or any other nephrocystin in humans.
引用
收藏
页码:371 / 375
页数:5
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