Molecular analysis of syndromic congenital heart disease using short tandem repeat markers and semiquantitative polymerase chain reaction method.
BACKGROUND
Velo-cardiofacial syndrome (VCFS) and DiGeorge syndrome (DGS) are developmental disorders characterized by craniofacial anomalies and conotruncal heart defects. Many of them have hemizygous deletions within chromosome 22q11.2, suggesting that haploinsufficiency in this region are responsible for their etiologies.


METHODS
To effectively understand the molecular basis for the chromosomal deletions, a semiquantitative fluores-cent polymerase chain reaction (PCR) method using 11 highly polymorphic markers located in 22q11.2 to perform genotyping analysis on 10 probands (five VCFS and five DGS) and their unaffected relatives were designed.


RESULTS
Two VCFS and four DGS patients have a 3-Mb deletion; the other DGS patient has a 1.5-Mb deletion and a cross-over occurs in the same interval at the other allele.


CONCLUSIONS
This results supports that the specific regions in 22q11.2 are susceptible to rearrangement and the deletions might be the genetic etiology of these syndromes. Most important of all, the new method, semiquantitative fluorescent PCR, is an effective method for detecting chromosomal microdeletions and has the following features: (i) the cost is inexpensive; (ii) the testing time is short; and (iii) the result is accurate.
Shi
Yi-Ru
YR
Department of Medical Research, China MedicalCollege Hospital, Taichung, Taiwan.
Hsieh
Kai-Sheng
KS
Wu
Jer-Yuarn
JY
Lee
Cheng-Chun
CC
Tsai
Chang-Hai
CH
Tsai
Fuu-Jen
FJ
D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D019465:Craniofacial Abnormalities / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D018598:Minisatellite Repeats; D016133:Polymerase Chain Reaction / Q000379:methods*; D020080:Tandem Repeat Sequences