PUBLICATION
Identification of a novel ARL13B variant in a Joubert syndrome-affected patient with retinal impairment and obesity
- Authors
- Thomas, S., Cantagrel, V., Mariani, L., Serre, V., Lee, J.E., Elkhartoufi, N., de Lonlay, P., Desguerre, I., Munnich, A., Boddaert, N., Lyonnet, S., Vekemans, M., Lisgo, S.N., Caspary, T., Gleeson, J., Attié-Bitach, T.
- ID
- ZDB-PUB-140821-8
- Date
- 2015
- Source
- European journal of human genetics : EJHG 23(5): 621-7 (Journal)
- Registered Authors
- Lee, Ji Eun
- Keywords
- none
- MeSH Terms
-
- ADP-Ribosylation Factors/chemistry
- ADP-Ribosylation Factors/genetics*
- ADP-Ribosylation Factors/metabolism
- Amino Acid Sequence
- Animals
- Brain/pathology
- Cerebellar Diseases/diagnosis*
- Cerebellar Diseases/genetics*
- Computational Biology
- Consanguinity
- Disease Models, Animal
- Eye Diseases, Hereditary/diagnosis*
- Eye Diseases, Hereditary/genetics*
- Genetic Linkage
- Homozygote
- Humans
- Immunohistochemistry
- Infant
- Magnetic Resonance Imaging
- Male
- Mice
- Models, Molecular
- Molecular Sequence Data
- Mutation*
- Obesity/diagnosis
- Obesity/genetics*
- Pedigree
- Phenotype*
- Protein Conformation
- Retinal Diseases/diagnosis
- Retinal Diseases/genetics*
- Sequence Alignment
- Sequence Analysis, DNA
- Zebrafish
- PubMed
- 25138100 Full text @ Eur. J. Hum. Genet.
Citation
Thomas, S., Cantagrel, V., Mariani, L., Serre, V., Lee, J.E., Elkhartoufi, N., de Lonlay, P., Desguerre, I., Munnich, A., Boddaert, N., Lyonnet, S., Vekemans, M., Lisgo, S.N., Caspary, T., Gleeson, J., Attié-Bitach, T. (2015) Identification of a novel ARL13B variant in a Joubert syndrome-affected patient with retinal impairment and obesity. European journal of human genetics : EJHG. 23(5):621-7.
Abstract
Joubert syndrome (JS) is a genetically heterogeneous autosomal recessive ciliopathy with 22 genes implicated to date, including a small, ciliary GTPase, ARL13B. ARL13B is required for cilia formation in vertebrates. JS patients display multiple symptoms characterized by ataxia due to the cerebellar vermis hypoplasia, and that can also include ocular abnormalities, renal cysts, liver fibrosis or polydactyly. These symptoms are shared with other ciliopathies, some of which display additional phenotypes, such as obesity. Here we identified a novel homozygous missense variant in ARL13B/JBTS8 in a JS patient who displayed retinal defects and obesity. We demonstrate the variant disrupts ARL13B function, as its expression did not rescue the mutant phenotype either in Arl13b(scorpion) zebrafish or in Arl13b(hennin) mouse embryonic fibroblasts, while the wild-type ARL13B did. Finally, we show that ARL13B is localized within the primary cilia of neonatal mouse hypothalamic neurons consistent with the known link between hypothalamic ciliary function and obesity. Thus our data identify a novel ARL13B variant that causes JS and retinopathy and suggest an extension of the phenotypic spectrum of ARL13B mutations to obesity.European Journal of Human Genetics advance online publication, 20 August 2014; doi:10.1038/ejhg.2014.156.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping