Contiguous mutation syndrome in the era of high‐throughput sequencing

We report on two siblings presenting the association of typical AP4‐deficiency neurological presentation and severe obesity with early onset. Using whole‐exome sequencing, we demonstrated that the siblings' phenotype results from the combined effects of two homozygous substitutions in AP4M1 and AZGP1 that account for the neurological signs and the morbid obesity of early onset, respectively. These two genes are located 170 kb apart on 7q22.1. We propose to broaden the concept of contiguous gene syndromes to phenotypes resulting from independent mutations in two genetically linked genes causing a contiguous mutation syndrome.

Source: Molecular Genetics & Genomic Medicine - March 1, 2015 Category: Genetics & Stem Cells Authors: Maéva Langouët, Karine Siquier‐Pernet, Sylvia Sanquer, Christine Bole‐Feysot, Patrick Nitschke, Nathalie Boddaert, Arnold Munnich, Grazia M. S. Mancini, Robert Barouki, Jeanne Amiel, Laurence Colleaux Tags: Original Article Source Type: research