Toward a genetic etiology of CHARGE syndrome: I. A systematic scan for submicroscopic deletions.
CHARGE syndrome is a distinctive subgroup within the more heterogeneous group of patients with CHARGE association. While significant progress has been made in the clinical delineation of this syndrome, the molecular basis of the disorder remains unknown. Based on the complex phenotype, some overlap with DiGeorge/velocardiofacial syndrome (DGS/VCFS), and its estimated population incidence, we hypothesized that CHARGE syndrome could be caused by an unidentified genomic microdeletion. In order to address this hypothesis, we carried out a genome-wide screen for loss of expected heterozygosity using 811 microsatellite markers in ten CHARGE syndrome subjects and their unaffected parents. Eight markers gave results suggestive of failure to inherit one parental allele. These loci were tested with fluorescence in situ hybridization (FISH), but none showed evidence of deletion. This screen sets upper limits on the length of a CHARGE-related microdeletion, should that be the genetic mechanism underlying the phenotype.
Lalani
Seema R
SR
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Stockton
David W
DW
Bacino
Carlos
C
Molinari
Laura M
LM
Glass
Nancy L
NL
Fernbach
Susan D
SD
Towbin
Jeffrey A
JA
Craigen
William J
WJ
Graham
John M
JM
Hefner
Margaret A
MA
Lin
Angela E
AE
McBride
Kim L
KL
Davenport
Sandra L
SL
Belmont
John W
JW
D000483:Alleles; D015139:Blotting, Southern; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000378:metabolism; D017353:Gene Deletion; D005819:Genetic Markers; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D010641:Phenotype; D011110:Polymorphism, Genetic; D013577:Syndrome
D018076:DNA, Complementary; D005819:Genetic Markers