Two patients with balanced translocations and autistic disorder: CSMD3 as a candidate gene for autism found in their common 8q23 breakpoint area

Abstract

Recent studies estimated a rate of 3-5% of cytogenetic abnormalities involving many different chromosomes in autistic spectrum disorders (ASDs). Here, we report on two unrelated male patients with de novo translocations, autistic behaviour and psychomotor delay. These two patients carry a balanced chromosome translocation t(5;8)(q14.3;q23.3) and t(6;8)(q13;q23.2), respectively. A detailed physical map covering the regions involved in the translocations was constructed using BAC clones mapping on chromosomes 5q14.3, 6q13 and 8q23. Fluorescence in situ hybridisation (FISH) analyses were carried out using these genomic clones. We fine mapped the two translocation breakpoints on chromosomes 8 identifying their position within a short 5 Mb genomic region. Breakpoints on chromosomes 8 in both patients do not interrupt any known gene but both map in a region containing the CSMD3 gene, which thereby can be considered as a candidate for ASDs.

MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations

“…Although MEF2C was deleted in only one of their three cases, a position effect on MEF2C of the two other deletions cannot be excluded. This hypothesis is emphasised by the report, in a patient sharing a strikingly similar phenotype, of a de novo balanced translocation between chromosomes 5 and 8, the breakpoint being located near the MEF2C gene 25. Moreover, Mef2c -null mice display behavioural phenotypes with abnormal anxiety, decreased cognitive function, and marked paw wringing/clasping stereotypy, resulting in a Rett-like phenotype as observed in mutant Mecp2 mouse models 23 24 26.…”

NRXN1 deletions identified by array comparative genome hybridisation in a clinical case series – further understanding of the relevance of NRXN1 to neurodevelopmental disorders

“…Patient 34 had developmental delay and autism, and in addition to an exon 19 NRXN1 deletion, also carried a chromosome 8 deletion resulting in intragenic deletion of CSMD3, a gene whose function is currently unknown, but which has been shown to be expressed in adult and fetal brain [37]. Floris et al [38] described two patients with autistic disorder and balanced translocations with breakpoints close to CSMD3 suggesting that this is a candidate gene for autism. Apart from infants less than 1 year old, only one patient (patient 15) had an exonic deletion with no reported neurodevelopmental problems: this patient was tested for amenorrhea and premature ovarian failure, and had a deletion of exons 4 to 5, suggesting that this specific deletion may not result in fully penetrant functional compromise of NRXN1.…”

Combined Analysis with Copy Number Variation Identifies Risk Loci in Lung Cancer

“…CCDC102B in 18q22.1 is associated with somatic mutations in lung cancer (1 mutated sample). Moreover, CSMD3 and CCDC102B have been reported to be affected by genomic rearrangement events in autistic patients [28] and in patients with diaphragmatic defects [29], respectively. Given the fact that these two genes in our neighboring gene list were reported with mutations in lung cancer, we expected other genes to be investigated in future studies.…”