A novel homozygous splice site mutation in NALCN identified in siblings with cachexia, strabismus, severe intellectual disability, epilepsy and abnormal respiratory rhythm

被引：29

作者：

Gal, Moran ^{[1
]}

Magen, Daniella ^{[2
,3
]}

Zahran, Younan ^{[4
]}

Ravid, Sarit ^{[9
,10
]}

Eran, Ayelet ^{[5
]}

Khayat, Morad ^{[6
]}

Gafni, Chen ^{[6
]}

Levanon, Erez Y. ^{[1
]}

Mandel, Hanna ^{[7
,8
]}

机构：

[1] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, Ramat Gan, Israel

[2] Rambam Hlth Care Campus, Pediat Nephrol Inst, Haifa, Israel

[3] Technion Israel Inst Technol, Rappaport Sch Med, Mol Med Lab, Haifa, Israel

[4] Clalit Hlth Serv, Dept Pediat Med, Ibillin, Israel

[5] Hlth Care Campus, Dept Radiol, Haifa, Israel

[6] Emek Med Ctr, Genet Inst, Afula, Israel

[7] Rambam Hlth Care Ctr, Metab Unit, Haifa, Israel

[8] Technion Israel Inst Technol, Rappaport Sch Med, Haifa, Israel

[9] Rambam Hlth Care Campus, Meyer Childrens Hosp, Pediat Neurol Unit, Haifa, Israel

[10] Rambam Hlth Care Campus, Meyer Childrens Hosp, Epilepsy Serv, Haifa, Israel

来源：

EUROPEAN JOURNAL OF MEDICAL GENETICS | 2016年 / 59卷 / 04期

基金：

以色列科学基金会;

关键词：

Cachexia; NALCN gene; Intellectual disability; Abnormal respiratory rhythm; Seizures; HYPOTONIA; CHANNEL; SODIUM; FACE;

D O I：

10.1016/j.ejmg.2016.02.007

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We studied three siblings, born to consanguineous parents who presented with severe intellectual disability, cachexia, strabismus, seizures and episodes of abnormal respiratory rhythm. Whole exome sequencing led to identification of a novel homozygous splice site mutation, IVS29-1G > A in the NALCN gene, that resulted in aberrant transcript in the patients. NALCN encodes a voltage-independent cation channel, involved in regulation of neuronal excitability. Three homozygous mutations in the NALCN gene were previously identified in only eight patients with severe hypotonia, speech impairment, cognitive delay, constipation and Infantile-Neuroaxonal-dystrophy- like symptoms. Our patients broaden the clinical spectrum associated with recessive mutations in NALCN, featuring also disrupted respiratory rhythm mimicking homozygous Nalcn knockout mice. (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：204 / 209

页数：6

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