M. Mannens et al., POSITIONAL CLONING OF GENES INVOLVED IN THE BECKWITH-WIEDEMANN SYNDROME, HEMIHYPERTROPHY, AND ASSOCIATED CHILDHOOD TUMORS, Medical and pediatric oncology, 27(5), 1996, pp. 490-494
The Beckwith-Wiedemann syndrome (BWS) is an overgrowth malformation sy
ndrome that occurs with an incidence of 1:13,700 births. There is a st
riking incidence of childhood tumors found in BWS patients. Various li
nes of investigation have localized ''imprinted'' genes involved in BW
S and associated childhood tumors to 11p15. High resolution mapping of
8 rare balanced chromosomal BWS rearrangements enabled us to identify
three distinct regions on chromosome 11p15 that might harbor genes in
volved in the above-mentioned disorders. These results suggest genetic
heterogeneity that correlates with the clinical heterogeneity seen in
the patients studied. Expressed candidate gene sequences from these r
egions have been cloned and parity sequenced. These transcripts are ei
ther disrupted by or are at least within a few kb of these BWS chromos
ome breakpoints. So far, zinc-finger sequences and one Kruppel-associa
ted box (KRAB) domain were found in independent candidate genes which
are compatible with a regulating function of growth promoting genes. T
he abundance of expression of these genes varies from low abundant in
all adult and fetal tissues tested to detectable on Northern blots of
adult tissues. In addition to our 11p15 studies we have analyzed addit
ional chromosome regions, in particular 1p. Cytogenetic, loss of heter
ozygosity (LOH) and comparative genomic hybridization (CGH) studies ha
ve identified 1p35 as a region of interest. A positional cloning effor
t to identify a balanced 1p35 translocation found in a Wilms tumor has
led to the isolation of a YAC, crossing this breakpoint. (C) 1996 Wil
ey-Liss, Inc.