Homozygous deletion of an 80 kb region comprising part of DNAJC6 and LEPR genes on chromosome 1P31.3 is associated with early onset obesity, mental retardation and epilepsy

作者：Vauthier Virginie; Jaillard Sylvie; Journel Hubert; Dubourg Christele; Jockers Ralf^*; Dam Julie

来源：Molecular Genetics and Metabolism, 2012, 106(3): 345-350.

DOI：10.1016/j.ymgme.2012.04.026

• Leptin receptor
• OB-RGRP/endospanin-1
• Epilepsy
• Obesity
• Auxilin-1

Context: The genomic organization of the LEPR gene is complex and generates three independent transcripts whose respective functions are still poorly understood. %26lt;br%26gt;Methods/results: We describe here a 7-year old patient with a homozygous 80 kb 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. %26lt;br%26gt;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.

• 出版日期2012-7