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

ABSTRACT 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‐...

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Published inHuman mutation Vol. 35; no. 3; pp. 289 - 293
Main Authors Borman, Arundhati Dev, Pearce, Laura R., Mackay, Donna S., Nagel-Wolfrum, Kerstin, Davidson, Alice E., Henderson, Robert, Garg, Sumedha, Waseem, Naushin H., Webster, Andrew R., Plagnol, Vincent, Wolfrum, Uwe, Farooqi, I. Sadaf, Moore, Anthony T.
Format Journal Article
LanguageEnglish
Published United States Blackwell Publishing Ltd 01.03.2014
Hindawi Limited
BlackWell Publishing Ltd
Subjects
Adaptor Proteins, Signal Transducing
Brief Reports
Child
Chromosome Mapping
cilia
Consanguinity
Eye Proteins - genetics
Female
Frameshift Mutation
Genes, Recessive
Homeostasis
Homozygote
Humans
Male
Mutation
Obesity
Obesity - genetics
Pedigree
Proteins - genetics
retinal dystrophy
Retinitis Pigmentosa - genetics
TUB
tubby
United Kingdom
Whites - genetics
United Kingdom
TUB
retinal dystrophy
tubby
cilia
obesity
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Summary:ABSTRACT 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. We report the first homozygous mutation in TUB associated with retinal dystrophy and obesity.
Bibliography:European Community - No. FP7/2009/241955 "SYSCILIA"
istex:7A38259F4A15B1B298B3CD2E9D9F1E8B96521AB2
Rosetrees Trust
Fight for Sight
ArticleID:HUMU22482
National Institute for Health Research (Moorfields Biomedical Research Centre and Cambridge Biomedical Research Centre)
Foundation Fighting Blindness (USA)
ark:/67375/WNG-2PP8KWJ7-Q
Wellcome Trust - No. 077016/Z/05/Z; No. 098497/Z/12/Z; No. 096106/Z/11/Z
The FAUN Foundation
Contract grant sponsors: Wellcome Trust (077016/Z/05/Z, 098497/Z/12/Z, 096106/Z/11/Z); National Institute for Health Research (Moorfields Biomedical Research Centre and Cambridge Biomedical Research Centre); Fight for Sight; Foundation Fighting Blindness (USA); the Rosetrees Trust; European Community (FP7/2009/241955 “SYSCILIA”); The FAUN Foundation (Germany).
These authors contributed equally to this work.
Communicated by Ravi Savarirayan
Correspondence to: Professor Anthony Moore, UCL Institute of Ophthalmology and Moorfields Eye Hospital London. E‐mail
tony.moore@ucl.ac.uk
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ISSN:1059-7794
1098-1004
DOI:10.1002/humu.22482