| Co-Investigator(Kenkyū-buntansha) |
MOMMA Kazuo Tokyo Women's Medical University, Pediatric Cardiology, Professor, 医学部, 教授 (80075233)
IMAMURA Shin-ichiro Tokyo Women's Medical University, Research Division, Assistant, 医学部, 助手 (00176497)
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| Research Abstract |
To investigate molecular and clinical aspects of conotruncal anomaly face (CAF), we studied the correlation between deletion size and phenotype and the mode of inheritance in 180 conotruncal anomaly face syndrome (CAFS) patients. In CAFS patients, the most frequently observed anomalies were tetralogy of Fallot (TOF) (74%). Conversely, in DiGeorge syndrome (DGS) probands with deletion of 22q11.2, the most frequent cardiovascular anomalies found were interruption of the aortic arch type B (41%), and TOF (29%).
Hemizygosity for a region of 22q11.2 was found in 180 (98%) of the patients with CAFS by fluorescent in situ hybridization (FISH), using 20 DiGeorge critical region probes. Ninety-one percent had a distal breakpoint (type-A), 4% had an intermediate breakpoint (type-B), 6% more proximal breakpoints (types C,D and E). All DGS and CAFS patients with schizophrenia fell into the type-A group. No familial cases were found among CAFS patients with absent thymus/DGS, which indicates that extragenic factors may play a role in the genesis of phenotypic variability, especially in patients with cardiovascular anomalies. Also, no difference in deletion size was found among the same family members in the familial CAFS cases, although they had different phenotypes (type-A : 53% ; type-B : 32% ; type-C : 16%). The findings of this study indicated that CAF was almost always associated with the deletion of 22q11.2.
The UFDIL gene was deleted in l80patients studied with 22q11.2 deletion, and a smaller deletion of approximately 20 kb that removed exons 1 to 3 of UFDIL was found in one individual with features typical of del 22q11.2 syndrome. These data suggest that UFDIL haploinsufficiency contributes to the congenital heart and craniofacial defects seen in 22q11.2 deletion.
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