Back to Search
Start Over
Homozygous deletion of an 80kb region comprising part of DNAJC6 and LEPR genes on chromosome 1P31.3 is associated with early onset obesity, mental retardation and epilepsy.: Homozygous deletion of the DNAJ6C and the LEPR gene
- Source :
- Molecular Genetics and Metabolism; Vol 106, Molecular Genetics and Metabolism, Molecular Genetics and Metabolism, 2012, 106 (3), pp.345-50. ⟨10.1016/j.ymgme.2012.04.026⟩, Molecular Genetics and Metabolism, Elsevier, 2012, 106 (3), pp.345-50. ⟨10.1016/j.ymgme.2012.04.026⟩
- Publication Year :
- 2012
- Publisher :
- Academic Press Inc., 2012.
-
Abstract
- International audience; CONTEXT: The genomic organization of the LEPR gene is complex and generates three independent transcripts whose respective functions are still poorly understood. METHODS/RESULTS: We describe here a 7-year old patient with a homozygous 80kb deletion in the chromosomal 1p31.3 region with early onset obesity, mental retardation and epilepsy. The deleted region comprises the proximal promoter and exons 1 and 2 of the LEPR gene and exons 5 to 19 of the DNAJC6 gene. The deletion leads to the deficiency of all canonical OB-R isoforms but maintains the B219 OB-R short isoforms controlled by the preserved second LEPR promoter. The DNAJC6 gene encodes auxilin-1, a protein required for clathrin-dependent recycling of synaptic vesicles in neurons that is possibly at the origin of the mental retardation and epilepsy phenotype. The obese phenotype and the absence of signaling-competent OB-R are consistent with previously reported individuals with OB-R deficiency. The deletion eliminates an additional transcript of the LEPR gene that encodes endospanin-1, a protein that has been genetically and biochemically linked to OB-R function. CONCLUSIONS: Our study confirms the phenotype of individuals with OB-R deficiency and postulates the effects of auxilin-1 deficiency (mental retardation/epilepsy) and endospanin-1 deficiency (OB-R specific functions) in humans.
- Subjects :
- Gene isoform
Adult
Male
Adolescent
Endocrinology, Diabetes and Metabolism
Context (language use)
Biology
Biochemistry
03 medical and health sciences
Exon
Epilepsy
0302 clinical medicine
Endocrinology
Intellectual Disability
Genetics
medicine
Humans
Obesity
Age of Onset
Child
Molecular Biology
Gene
[SDV.BDD]Life Sciences [q-bio]/Development Biology
Auxilin-1
030304 developmental biology
Genomic organization
Sequence Deletion
0303 health sciences
[SDV.GEN]Life Sciences [q-bio]/Genetics
Leptin receptor
Homozygote
HSP40 Heat-Shock Proteins
Middle Aged
medicine.disease
Phenotype
OB-RGRP/endospanin-1
Chromosomes, Human, Pair 1
Child, Preschool
Receptors, Leptin
Female
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 10967192 and 10967206
- Volume :
- 106
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Molecular Genetics and Metabolism
- Accession number :
- edsair.doi.dedup.....13368a692d282fc22bec32d0f9231d7d
- Full Text :
- https://doi.org/10.1016/j.ymgme.2012.04.026