Phenotypic variability of atypical 22q11.2 deletions not including TBX1.
Interstitial deletions of the chromosome 22q11.2 region are the most common microdeletions in humans. The TBX1 gene is considered to be the major candidate gene for the main features in 22q11.2 deletion syndrome, including congenital heart malformations, (para)thyroid hypoplasia, and craniofacial abnormalities. We report on eight patients with atypical deletions of chromosome 22q11.2. These deletions comprise the distal part of the common 22q11.2 deleted region but do not encompass the TBX1 gene. Ten similar patients with overlapping distal 22q11.2 deletions have been reported previously. The clinical features of these patients are described and compared to those found in the classic 22q11.2 deletion syndrome. We discuss the possible roles of a position effect or haploinsufficiency of distally located genes (e.g., CRKL) in the molecular pathogenesis of the 22q11.2 deletion syndrome.
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Judith M A
JM
Verhagen
Karin E M
KE
Diderich
Grétel
G
Oudesluijs
Grazia M S
GM
Mancini
Alex J
AJ
Eggink
Anna C
AC
Verkleij-Hagoort
Irene A L
IA
Groenenberg
Patrick J
PJ
Willems
Frederik A
FA
du Plessis
Stella A
SA
de Man
Malgorzata I
MI
Srebniak
Diane
D
van Opstal
Lorette O M
LO
Hulsman
Laura J C M
LJ
van Zutven
Marja W
MW
Wessels
D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000473:pathology; D004062:DiGeorge Syndrome / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D011247:Pregnancy; D020825:T-Box Domain Proteins / Q000235:genetics*
D020825:T-Box Domain Proteins; C108625:TBX1 protein, human