How to Cite this Article: Barber JCK, Huang S, Bateman MS, Collins AL. 2011. Transmitted deletions of medial 5p and learning difficulties; Does the cadherin cluster only become penetrant when flanking genes are deleted? Am J Med Genet Part A 155: 2807–2815.
Transmitted deletions of medial 5p and learning difficulties; Does the cadherin cluster only become penetrant when flanking genes are deleted?†
Article first published online: 30 SEP 2011
Copyright © 2011 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 155, Issue 11, pages 2807–2815, November 2011
How to Cite
Barber, J. C.K., Huang, S., Bateman, M. S. and Collins, A. L. (2011), Transmitted deletions of medial 5p and learning difficulties; Does the cadherin cluster only become penetrant when flanking genes are deleted?. Am. J. Med. Genet., 155: 2807–2815. doi: 10.1002/ajmg.a.34241
- Issue published online: 20 OCT 2011
- Article first published online: 30 SEP 2011
- Manuscript Accepted: 10 JUL 2011
- Manuscript Received: 3 MAR 2011
- Department of Health (UK) [to SH]
- pair 5;
- chromosome deletion;
- learning disability;
- intellectual disability;
- candidate genes;
- cadherin genes;
- transmitted imbalance;
- DNA array
The central portion of the short arm of chromosome 5 is unusual in that large, cytogenetically visible interstitial deletions segregate in families with and without phenotypic consequences. Here we present a family in which a transmitted interstitial deletion of 5p13.3 to 5p14.3 co-segregated with learning and/or behavioral difficulties in six family members. Facial dysmorphism was not striking but a father and daughter both had lacrimal fistulae. The deletion was 12.23 Mb in size (chr5:20,352,535–32,825,775) and contained fifteen known protein coding genes. Five of these (GOLPH3; MTMR12; ZFR; SUB1; and NPR3) and an ultra-conserved microRNA (hsa-miR-579) were present in an 883 kb candidate gene region in 5p13.3 that was deleted in the present family but not in previously reported overlapping benign deletions. Members of the cadherin precursor gene cluster, with brain specific expression, were deleted in both affected and benign deletion families. The candidate genes in 5p13.3 may be sufficient to account for the consistent presence or absence of phenotype in medial 5p deletions. However, we consider the possibility of position effects in which CDH6, and/or other cadherin genes, become penetrant when adjacent genes, or modifiers of gene expression, are also deleted. This could account for the absence of intellectual disability in benign deletions of the cadherin cluster, the cognitive phenotype in medial 5p deletion syndrome and the greater severity of intellectual disability in patients with cri-du-chat syndrome and deletions of 5p15 that extend into the region deleted in the present family. © 2011 Wiley Periodicals, Inc.