Human Mutation · 2013 · 78 citations · 17 references
MedicineGeneticsMolecular GeneticsHuman GeneticsMedical GeneticsPediatric GeneticsGenetic DisordersInherited Retinal DystrophiesMendelian DisordersPediatric Retinal DisordersRetinal DisordersRetinal PathologyAutozygosity MappingChildhood BlindnessFrameshift MutationsHereditary Retinal DiseasePediatric Retinal DystrophiesRetinal Dystrophy GenesRetinal Dystrophy GeneticsWhole Exome Sequencing Studies
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.
17
Identification and Characterization of the Mouse Obesity Gene tubby: A Member of a Novel Gene Family
Patrick W. Kleyn, Wei Fan, Steve G. Kovats et al. · Cell · 1996 · 381 citations · Full text
A candidate gene for the mouse mutation tubby
Konrad Noben‐Trauth, Juergen K. Naggert, Michael North et al. · Nature · 1996 · 365 citations