Familial 22q11.2 deletions in DiGeorge/velocardiofacial syndrome are predominantly smaller than the commonly observed 3Mb.
OBJECTIVE
DiGeorge/velocardiofacial syndrome (DG/VCFS) is the most common cytogenetically characterized microdeletion of 22q11.2 region. In approximately 90% of patients, the deletion size is 3 Mb, whereas the remaining range from 1.5 to 2.5 Mb. The purpose of this study was to test the hypothesis that small deletions may be more easily tolerated in a familial fashion than larger deletions, especially for this syndrome.


METHODS
Sixteen FISH probes designed from bacterial artificial chromosomes (BACs) and P1 artificial chromosomes (PACs) mapped to 22q11.2 were used to determine the deletion sizes in 22 individuals from ten families with familial 22q11.2 deletion detected by standard FISH tests.


RESULTS
Seven families had deletions of < 3 Mb ( approximately 1.5 Mb) in size and 3 families had the common 3-Mb deletion. The 70% frequency of smaller sized deletions among this group of patients with familial del(22)(q11.2) is significantly higher than that reported among unselected group of patients with del(22)(q11.2) (P < 0.0001, Fisher exact test).


CONCLUSIONS
Familial del(22)(q11.2) are predominantly smaller than the common deletion size of 3 Mb, indicating that there may be some underlying mechanisms that favor parent-to-child transmission of smaller deletions in individuals with del(22)(q11.2), therefore, underscoring the need to exclude a familial basis in cases of del(22)(q11.2) smaller than 3 Mb.
Adeyinka
Adewale
A
Cytogenetics Laboratory Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Stockero
Kimberly J
KJ
Flynn
Heather C
HC
Lorentz
Cindy P
CP
Ketterling
Rhett P
RP
Jalal
Syed M
SM
D002872:Chromosome Deletion; D025063:Chromosome Disorders; D022202:Chromosomes, Artificial, Bacterial; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male