Dataset Information

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.

SUBMITTER: Borman AD

PROVIDER: S-EPMC4284018 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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A homozygous mutation in the TUB gene associated with retinal dystrophy and obesity.

Borman Arundhati Dev AD Pearce Laura R LR Mackay Donna S DS Nagel-Wolfrum Kerstin K Davidson Alice E AE Henderson Robert R Garg Sumedha S Waseem Naushin H NH Webster Andrew R AR Plagnol Vincent V Wolfrum Uwe U Farooqi I Sadaf IS Moore Anthony T AT

Human mutation 20131220 3

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 si ...[more]

PMID: 24375934

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Project description:ImportanceThe patients evaluated in this study, to our knowledge, represent the first complete clinical description of a family with an autosomal dominant inheritance pattern of retinal dystrophy associated with a novel mutation in RAX2.ObjectivesTo clinically evaluate 4 patients and 5 unaffected family members, characterize the disease phenotype over time, and identify the associated genetic mutation.Design, setting, and participantsA prospective, longitudinal, observational, case-series analysis of 9 members of an affected family at the Casey Eye Institute, Oregon Health and Science University, Portland. The dates of the study were from July 31, 1992, to August 11, 2014.InterventionsClinical evaluations included eye examination, color fundus photography, autofluorescence imaging, spectral-domain optical coherence tomography, kinetic visual field testing, and electroretinography. Genetic mutation screening was performed with next-generation sequencing, and identified mutations were confirmed with Sanger sequencing.Main outcomes and measuresClinical diagnosis and longitudinal characterization of retinal dystrophy and identification of genetic mutation.ResultsSix members of the family were identified as having retinal dystrophy (4 were examined, and 3 were genetically tested). Five unaffected family members were clinically evaluated (2 were genetically tested). The age at onset of retinal dystrophy was variable. All affected individuals presented with declining visual acuity, central scotomas, waxy disc pallor, attenuated vasculature, small yellow macular deposits and/or macular pigment mottling, and abnormal electroretinograms demonstrating mixed cone and rod dysfunction and a scotopic electronegative response to bright flashes. There were no other causes of an electronegative electroretinogram identified in any of the affected patients. Genetic testing revealed, to our knowledge, a novel frameshift heterozygous mutation in RAX2 in the patients with retinal dystrophy.Conclusions and relevanceA frameshift heterozygous mutation in RAX2 inherited in an autosomal dominant fashion was associated with mixed cone and rod dysfunction. Among the patients, there was variability in the age at onset and in the specific pattern of photoreceptor dysfunction, but the clinical course was nevertheless slowly progressive. Screening for RAX2 mutation could provide prognostic value for patients and families with scotopic electronegative responses to bright flashes.

Dataset Information

A homozygous mutation in the TUB gene associated with retinal dystrophy and obesity.

Publications

A homozygous mutation in the TUB gene associated with retinal dystrophy and obesity.

Similar Datasets

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