Unambiguous molecular detections with multiple genetic approach for the complicated chromosome 22q11 deletion syndrome.
BACKGROUND
Chromosome 22q11 deletion syndrome (22q11DS) causes a developmental disorder during the embryonic stage, usually because of hemizygous deletions. The clinical pictures of patients with 22q11DS vary because of polymorphisms: on average, approximately 93% of affected individuals have a de novo deletion of 22q11, and the rest have inherited the same deletion from a parent. Methods using multiple genetic markers are thus important for the accurate detection of these microdeletions.


METHODS
We studied 12 babies suspected to carry 22q11DS and 18 age-matched healthy controls from unrelated Taiwanese families. We determined genomic variance using microarray-based comparative genomic hybridization (array-CGH), quantitative real-time polymerase chain reaction (qPCR) and multiplex ligation-dependent probe amplification (MLPA).


RESULTS
Changes in genomic copy number were significantly associated with clinical manifestations for the classical criteria of 22q11DS using MPLA and qPCR (p < 0.01). An identical deletion was shown in three affected infants by MLPA. These reduced DNA dosages were also obtained partially using array-CGH and confirmed by qPCR but with some differences in deletion size.


CONCLUSIONS
Both MLPA and qPCR could produce a clearly defined range of deleted genomic DNA, whereas there must be a deleted genome that is not distinguishable using MLPA. These data demonstrate that such multiple genetic approaches are necessary for the unambiguous molecular detection of these types of complicated genomic syndromes.
Yang
Chen
C
Division of Genetics, Department of Pediatrics, Taipei Medical University Hospital, Taipei 11031, Taiwan. yeungsann@yahoo.com.tw
Huang
Cheng-Hung
CH
Cheong
Mei-Leng
ML
Hung
Kun-Long
KL
Lin
Lung-Huang
LH
Yu
Yeong-Seng
YS
Chien
Chih-Cheng
CC
Huang
Huei-Chen
HC
Chen
Chan-Wei
CW
Huang
Chi-Jung
CJ
D000015:Abnormalities, Multiple / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D017931:DNA Primers; D005260:Female; D005819:Genetic Markers; D015894:Genome, Human; D006330:Heart Defects, Congenital / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D022521:Ligase Chain Reaction; D008297:Male; D016133:Polymerase Chain Reaction; D013577:Syndrome; D013624:Taiwan
D017931:DNA Primers; D005819:Genetic Markers