6533b853fe1ef96bd12acbba
RESEARCH PRODUCT
A homozygous mutation in the TUB gene associated with retinal dystrophy and obesity.
Andrew R. WebsterNaushin WaseemLaura R. PearceRobert H. HendersonKerstin Nagel-wolfrumDonna S. MackayAlice E. DavidsonArundhati Dev BormanAnthony T. MooreSumedha GargVincent PlagnolUwe WolfrumI. Sadaf Farooqisubject
ProbandMaleobesity030209 endocrinology & metabolismGenes RecessiveConsanguinityBiologymedicine.disease_causeWhite PeopleFrameshift mutation03 medical and health sciencesConsanguinity0302 clinical medicineRetinitis pigmentosaGeneticsRod-cone dystrophymedicineHomeostasisHumansretinal dystrophyTUBChildEye ProteinsFrameshift MutationGenetics (clinical)030304 developmental biologyAdaptor Proteins Signal TransducingGenetics0303 health sciencesMutationHomozygoteChildhood blindnessciliatubbyChromosome MappingProteinsmedicine.diseaseUnited Kingdom3. Good healthPedigreeBrief ReportsFemaleRetinal DystrophiesRetinitis Pigmentosadescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-12-20 |