title: 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-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.
authors.affiliation: Moorfield's Eye Hospital, London, EC1C 2PD, UK; Institute of Ophthalmology, London, EC1V 9EL, UK.
authors.forename: Arundhati Dev
authors.initials: AD
authors.lastname: Borman
authors.forename: Laura R
authors.initials: LR
authors.lastname: Pearce
authors.forename: Donna S
authors.initials: DS
authors.lastname: Mackay
authors.forename: Kerstin
authors.initials: K
authors.lastname: Nagel-Wolfrum
authors.forename: Alice E
authors.initials: AE
authors.lastname: Davidson
authors.forename: Robert
authors.initials: R
authors.lastname: Henderson
authors.forename: Sumedha
authors.initials: S
authors.lastname: Garg
authors.forename: Naushin H
authors.initials: NH
authors.lastname: Waseem
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.forename: Uwe
authors.initials: U
authors.lastname: Wolfrum
authors.forename: I Sadaf
authors.initials: IS
authors.lastname: Farooqi
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002648:Child; D002874:Chromosome Mapping; D003241:Consanguinity; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006706:Homeostasis; D006720:Homozygote; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics*; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D006113:United Kingdom; D044465:White People / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005136:Eye Proteins; D011506:Proteins; C508878:TUB protein, human; C105443:TULP1 protein, human
keywords: TUB; cilia; obesity; retinal dystrophy; tubby