Sacral agenesis: a pilot whole exome sequencing and copy number study

Porsch, R. M. et al. (2016) Sacral agenesis: a pilot whole exome sequencing and copy number study. BMC Medical Genetics, 17(1), 98. (doi: 10.1186/s12881-016-0359-2) (PMID:28007035) (PMCID:PMC5178083)

Abstract

Background: Caudal regression syndrome (CRS) or sacral agenesis is a rare congenital disorder characterized by a constellation of congenital caudal anomalies affecting the caudal spine and spinal cord, the hindgut, the urogenital system, and the lower limbs. CRS is a complex condition, attributed to an abnormal development of the caudal mesoderm, likely caused by the effect of interacting genetic and environmental factors. A well-known risk factor is maternal type 1 diabetes. Method: Whole exome sequencing and copy number variation (CNV) analyses were conducted on 4 Caucasian trios to identify de novo and inherited rare mutations. Results: In this pilot study, exome sequencing and copy number variation (CNV) analyses implicate a number of candidate genes, including SPTBN5, MORN1, ZNF330, CLTCL1 and PDZD2. De novo mutations were found in SPTBN5, MORN1 and ZNF330 and inherited predicted damaging mutations in PDZD2 (homozygous) and CLTCL1 (compound heterozygous). Importantly, predicted damaging mutations in PTEN (heterozygous), in its direct regulator GLTSCR2 (compound heterozygous) and in VANGL1 (heterozygous) were identified. These genes had previously been linked with the CRS phenotype. Two CNV deletions, one de novo (chr3q13.13) and one homozygous (chr8p23.2), were detected in one of our CRS patients. These deletions overlapped with CNVs previously reported in patients with similar phenotype. Conclusion: Despite the genetic diversity and the complexity of the phenotype, this pilot study identified genetic features common across CRS patients.

• Item Type: Articles
• Additional Information: Seed Funding Programme for Basic Research, University of Hong Kong, Project Code:201410159002 to MMGB. Small Project Funding, University of Hong Kong, Project Code 201209176012 to DC. EM; PDM, VC would like to acknowledge Ricerca Corrente Ministero della Salute Italia 5× Mille, Aletti- Volpati Trust Onlus and private funding resources.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Campbell, Dr Desmond
• Authors: Porsch, R. M., Merello, E., De Marco, P., Cheng, G., Rodriguez, L., So, M., Sham, P. C., Tam, P. K., Capra, V., Cherny, S. S., Garcia-Barcelo, M.-M., and Campbell, D. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: BMC Medical Genetics
• Publisher: BioMed Central Ltd.
• ISSN: 1471-2350
• ISSN (Online): 1471-2350
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in BMC Medical Genetics 17(1):98
• Publisher Policy: Reproduced under a Creative Commons License