Recurrent 22q11.2 deletion in a sibship suggestive of parental germline mosaicism in velocardiofacial syndrome

Abstract

Deletions of chromosome 22q11.2 are recognized as the main cause of a number of clinical phenotypes, including velocardiofacial syndrome (VCFS) and DiGeorge syndrome (DGS). Velocardiofacial syndrome is a relatively common developmental disorder that is characterized by craniofacial anomalies and conotruncal heart defects. Most 22q11.2 deletions occur sporadically, although the deletion may be transmitted in some cases. The present performed a molecular analysis in one family including a patient with clinical diagnosis of VCFS and his sister with a suggestive phenotype. Six polymorphic 22q11.2 markers (i.e. D22S420, D22S264, D22S941, D22S306, D22S425 and D22S257) were used for genotype analysis of the DNA from the patients and unaffected relatives. The results revealed a 22q11.2 deletion in the patient and his sister from one of six markers (i.e. D22S941). Genotype analysis demonstrated that the deletion in this sib was of maternal origin. The results suggest that the mother probably has gonadal mosaicism. The other relatives present normal DNA profiles for all markers. These results have implications for genetic counseling because of a risk of transmission by germ cells carrying the deletion, even when parents present with a normal DNA profile in their blood cells.