Interstitial deletion of 10p and atrial septal defect in DiGeorge 2 syndrome
- 25 June 2004
- journal article
- Published by Wiley in Clinical Genetics
- Vol. 66 (2), 128-136
- https://doi.org/10.1111/j.1399-0004.2004.00290.x
Abstract
We present molecular genetic investigations of a 4-year-old boy with craniofacial dysmorphism and developmental delay. Trivial mitral and tricuspid regurgitation without gross structural abnormality was diagnosed by echocardiography. High-resolution chromosome analysis revealed an interstitial deletion, del(10)(p12.1p12.32). To characterize the deletion size and breakpoints, we performed fluorescence in situ hybridization analysis using 27 BAC clones. Our data demonstrate an approximately 5.5 Mb deletion del(10)(p12.1p12.31). Surprisingly, the BAC clone RP11-56H7 that contains NEBL, an apparent downstream gene of the cardiogenic transcription factor HAND2 previously shown to be deleted in the patients with DiGeorge 2 syndrome and 10p13 deletion, was deleted in our patient with 10p12.1-p12.31 deletion. In addition, we provide clinical data and results of molecular analysis for a patient with multiple congenital anomalies including Ebstein's anomaly, kidney malformations, and 10p13-p14 deletion. We also reviewed 19 patients with congenital heart defects and deletions involving 10p and propose that atrial septal defect (ASD) is a common cardiac anomaly associated with DiGeorge 2 syndrome. Based on genotype-phenotype analysis of published patients and those reported herein, we propose an approximately 1.0 Mb critical region between loci D10S547 and D10S2176 in 10p14 to be associated with ASD. Considering that septal defects are the most frequent congenital heart anomaly, we suggest that further investigations in the 10p critical region are important to identify gene(s) responsible for this common birth defect.Keywords
This publication has 45 references indexed in Scilit:
- A HANDful of questions: the molecular biology of the heart and neural crest derivatives (HAND)-subclass of basic helix–loop–helix transcription factorsGene, 2003
- Two novel frameshift mutations in NKX2.5 result in novel features including visceral inversus and sinus venosus type ASDJournal of Medical Genetics, 2002
- GATA3 haplo-insufficiency causes human HDR syndromeNature, 2000
- MRI findings in a patient with partial monosomy 10p.Journal of Medical Genetics, 1998
- DiGeorge anomaly and chromosome 10p deletions: One or two loci?American Journal of Medical Genetics, 1997
- Cardiac anomalies associated with a chromosome 22q11 deletion in patients with conotruncal anomaly face syndromeThe American Journal of Cardiology, 1996
- Deletion of the short arm of chromosome 10 (10p13): Report of a patient and reviewAmerican Journal of Medical Genetics, 1994
- DiGeorge anomaly associated with 10p deletionAmerican Journal of Medical Genetics, 1991
- Hypoparathyroidism and T cell immune defect in a patient with 10p deletion syndromeThe Journal of Pediatrics, 1986
- Partial monosomy of chromosome 10 short arms.Journal of Medical Genetics, 1983