A Homozygous Mutation in the TUB Gene Associated with Retinal Dystrophy and Obesity

被引：50

作者：

Borman, Arundhati Dev ^{[1
,2
]}

Pearce, Laura R. ^{[3
]}

Mackay, Donna S. ^{[2
]}

Nagel-Wolfrum, Kerstin ^{[4
]}

Davidson, Alice E. ^{[2
]}

Henderson, Robert ^{[2
]}

Garg, Sumedha ^{[3
]}

Waseem, Naushin H. ^{[2
]}

Webster, Andrew R. ^{[1
,2
]}

Plagnol, Vincent ^{[5
]}

Wolfrum, Uwe ^{[4
]}

Farooqi, I. Sadaf ^{[3
]}

Moore, Anthony T. ^{[1
,2
]}

机构：

[1] Moorfields Eye Hosp, London EC1C 2PD, England

[2] Inst Ophthalmol, London EC1V 9EL, England

[3] Univ Cambridge, Metab Res Labs, Wellcome Trust MRC Inst Metab Sci, Addenbrookes Hosp, Cambridge CB2 0QQ, England

[4] Johannes Gutenberg Univ Mainz, Inst Zool, Dept Cell & Matrix Biol, Mainz, Germany

[5] UCL, Genet Inst, London WC1E 6BT, England

来源：

HUMAN MUTATION | 2014年 / 35卷 / 03期

基金：

英国惠康基金;

关键词：

TUB; tubby; retinal dystrophy; obesity; cilia; LEBER CONGENITAL AMAUROSIS; RETINITIS-PIGMENTOSA; RECESSIVE MUTATIONS; DEGENERATION; PROTEIN-1; FAMILY; MOUSE; IDENTIFICATION; TRAFFICKING; EXPRESSION;

D O I：

10.1002/humu.22482

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Inherited retinal dystrophies are a major cause of childhood blindness. Here, we describe the identification of a homozygous frameshift mutation (c.1194_1195delAG, p.Arg398Serfs*9) in TUB in a child from a consanguineous UK Caucasian family investigated using autozygosity mapping and whole-exome sequencing. The proband presented with obesity, night blindness, decreased visual acuity, and electrophysiological features of a rod cone dystrophy. The mutation was also found in two of the proband's siblings with retinal dystrophy and resulted in mislocalization of the truncated protein. In contrast to known forms of retinal dystrophy, including those caused by mutations in the tubby-like protein TULP-1, loss of function of TUB in the proband and two affected family members was associated with early-onset obesity, consistent with an additional role for TUB in energy homeostasis. Hum Mutat 35:289.293, 2014. Published 2013 Wiley Periodicals, Inc.

引用

页码：289 / 293

页数：5

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