ORIGINAL PAPER
Human EGFR, a candidate gene for the
Silver-Russell syndrome, is biallelically
expressed in a wide range of fetal tissues
Emma L Wakeling
1,2
, Sayeda N Abu-Amero
1
, Philip Stanier
1
, Michael A Preece
1,2
and
Gudrun E Moore
1
1
A ction Research L aboratory for the Molecular Biology of Fetal Development, Division of Paediatrics, Obstetrics
and Gynaecology, Imperial College School of Medicine, Queen Charlotte’s and Chelsea Hospital, London, UK
2
Institute of Child Health, University of London, UK
Maternal uniparental disomy of chromosome 7 (mUPD7) has been reported in
around 10% of cases of Silver-Russell syndrome (SRS). This suggests that at
least one gene on chromosome 7 is imprinted and involved in the pathogenesis
of this condition. One candidate is epidermal growth factor receptor ( EGFR)
which maps to chromosome 7p12, a region homologous to an imprinted region
on mouse chromosome 11. Using a restriction fragment length polymorphism,
biallelic expression of EGFR was found in a range of normal human fetal
tissues. Expression was also demonstrated in fibroblasts and lymphoblasts
from SRS patients with mUPD7. Thus no evidence that EGFR is imprinted was
found, making its involvement in SRS unlikely. However, EGFR was shown to
be widely expressed in the human fetus, evidence that this gene plays an
important role in early development.
Keywords: epidermal growth factor receptor; Silver-Russell syndrome;
maternal uniparental disomy; imprinting; fetal expression
Introduction
Maternal uniparental disomy for chromosome 7
(mUPD7) has been described in several patients with
intrauterine growth retardation (IUGR).
1–3
More
recently, approximately 10% of cases of Silver-Russell
syndrome (SRS) have also been found to be associated
with mUPD7.
4,5
SRS is characterised by intrauterine
and postnatal growth retardation with relative sparing
of cranial growth, triangular facies and downturned
corners of the mouth. In a large proportion fifth finger
clinodactyly and facial, limb or truncal asymmetry is
also present. In five SRS patients with mUPD7 studied
by our group, no consistently isodisomic areas have
been found (unpublished observation). This makes
exposure of a recessive gene an unlikely explanation
for the phenotype associated with mUPD7, suggesting
instead that one or more gene(s) on chromosome 7 are
imprinted and play a role in the pathogenesis of SRS
and IUGR in some cases.
Likely imprinted candidate genes can be sought by
comparison of mouse and human linkage maps. Several
Correspondence: Dr E Wakeling, Action Research Labo-
ratory for the Molecular Biology of Fetal Development,
Division of Paediatrics, Obstetrics and Gynaecology, Imperial
College School of Medicine, Queen Charlotte’s and Chelsea
Hospital, Goldhawk Road, London W6 0XG, UK. Fax: +44
181 383 1838; Tel: + 44 181 383 3533;
E-mail: e.wakeling@rpms.ac.uk
Received 30 January 1997; revised 6 October 1997; accepted
24 November 1997
Journal: European Journal of Human Genetics Article: 5200179
European Journal of Human Genetics (1998) 6, 158–164
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