Identification of critical regions and candidate genes for cardiovascular malformations and cardiomyopathy associated with deletions of chromosome 1p36.
Cardiovascular malformations and cardiomyopathy are among the most common phenotypes caused by deletions of chromosome 1p36 which affect approximately 1 in 5000 newborns. Although these cardiac-related abnormalities are a significant source of morbidity and mortality associated with 1p36 deletions, most of the individual genes that contribute to these conditions have yet to be identified. In this paper, we use a combination of clinical and molecular cytogenetic data to define five critical regions for cardiovascular malformations and two critical regions for cardiomyopathy on chromosome 1p36. Positional candidate genes which may contribute to the development of cardiovascular malformations associated with 1p36 deletions include DVL1, SKI, RERE, PDPN, SPEN, CLCNKA, ECE1, HSPG2, LUZP1, and WASF2. Similarly, haploinsufficiency of PRDM16-a gene which was recently shown to be sufficient to cause the left ventricular noncompaction-SKI, PRKCZ, RERE, UBE4B and MASP2 may contribute to the development of cardiomyopathy. When treating individuals with 1p36 deletions, or providing prognostic information to their families, physicians should take into account that 1p36 deletions which overlie these cardiac critical regions may portend to cardiovascular complications. Since several of these cardiac critical regions contain more than one positional candidate gene-and large terminal and interstitial 1p36 deletions often overlap more than one cardiac critical region-it is likely that haploinsufficiency of two or more genes contributes to the cardiac phenotypes associated with many 1p36 deletions.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
Hitisha P
HP
Zaveri
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
Tyler F
TF
Beck
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
Andrés
A
Hernández-García
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
Katharine E
KE
Shelly
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Tara
T
Montgomery
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Arie
A
van Haeringen
Clinical Genetic Department, Karolinska University Hospital and Institution of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Britt-Marie
BM
Anderlid
Department of Clinical Genetics, Birmingham Women's Hospital, Birmingham, United Kingdom.
Chirag
C
Patel
Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia.
Himanshu
H
Goel
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
Gunnar
G
Houge
Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Bernice E
BE
Morrow
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
Sau Wai
SW
Cheung
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
Seema R
SR
Lalani
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
Daryl A
DA
Scott
D018376:Cardiovascular Abnormalities / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D017353:Gene Deletion; D006801:Humans