Cardiac phenotypes in chromosome 4q- syndrome with and without a deletion of the dHAND gene.
OBJECTIVE
Terminal deletions of chromosome 4q are commonly associated with cardiovascular malformations (CVMs). The dHAND gene (HAND2 heart and neural crest derivative express 2), a basic helix-loop-helix transcription factor expressed in the developing heart, maps to 4q33. A targeted deletion in mouse shows that dHAND plays an important role in heart development, suggesting that haploinsufficiency of in patients with 4q deletions may be causal for CVMs. The purpose of this study is to examine the possible association between dHAND haploinsufficiency with the CVMs that occur in patients with 4q terminal deletions.


METHODS
Fluorescence in situ hybridization (FISH) was performed with a dHAND human genomic probe on five patients with terminal deletion at 4q33 or 4q34.


RESULTS
Of the three patients with a deletion of the dHAND locus, two had CVM (both valvar pulmonic stenosis). Of the two patients without a deletion of the dHAND gene, one had a small atrial septal defect noted on autopsy. In one of the patients with breakpoint on chromosome 4 assigned to 4q34.2 by GTG-banding, FISH revealed deletion of the dHAND gene.


CONCLUSIONS
The results suggest that cardiac phenotypes are very variable in patients with the terminal deletion of chromosome 4q and that haploinsufficiency of the dHAND is not necessarily associated with CVMs. The correct cytogenetic interpretation of terminal chromosome deletions might be augmented by FISH.
Huang
Taosheng
T
Division of Genetics, Department of Pediatrics, University California, Irvine, California 92697, USA.
Lin
Angela E
AE
Cox
Gerald F
GF
Golden
Wendy L
WL
Feldman
Gerald L
GL
Ute
Moog
M
Schrander-Stumpel
Connie
C
Kamisago
Mitsuhiro
M
Vermeulen
Stefan J T
SJ
D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002894:Chromosomes, Human, Pair 4; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D008297:Male; D014157:Transcription Factors / Q000235:genetics*; D029961:Zebrafish Proteins
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C498765:HAND2 protein, human; C410915:hand2 protein, zebrafish