Position effect leading to haploinsufficiency in a mosaic ring chromosome 14 in a boy with autism

Castermans, Dries; Thienpont, Bernard; Volders, Karolien; Crepel, An; Vermeesch, Joris; Schrander-Stumpel, Connie T; Van de Ven, Willem; Steyaert, Jean; Creemers, John; Devriendt, Koenraad

doi:10.1038/ejhg.2008.71

Position effect leading to haploinsufficiency in a mosaic ring chromosome 14 in a boy with autism

Author:

Castermans, Dries

Thienpont, Bernard ; Volders, Karolien ; Crepel, An ; Vermeesch, Joris ; Schrander-Stumpel, Connie T ; Van de Ven, Willem ; Steyaert, Jean ; Creemers, John ; Devriendt, Koenraad

Keywords:

Adolescent, Autistic Disorder, Chromosome Breakage, Chromosomes, Human, Pair 14, Cloning, Molecular, Gene Duplication, Haploidy, Humans, Male, Mosaicism, Translocation, Genetic, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Genetics & Heredity, autism, mosaic ring chromosome 14, position effect, amisyn, SPECTRUM DISORDERS, MEMBRANE-FUSION, TRANSLOCATION, GENE, DISRUPTION, MECHANISMS, DELETION, DISEASE, PROTEIN, AMISYN, 0604 Genetics, 1103 Clinical Sciences, 3105 Genetics, 3202 Clinical sciences

Abstract:

We describe an individual with autism and a coloboma of the eye carrying a mosaicism for a ring chromosome consisting of an inverted duplication of proximal chromosome 14. Of interest, the ring formation was associated with silencing of the amisyn gene present in two copies on the ring chromosome and located at 300 kb from the breakpoint. This observation lends further support for a locus for autism on proximal chromosome 14. Moreover, this case suggests that position effects need to be taken into account, when analyzing genotype-phenotype correlations based on chromosomal imbalances.