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Analysis of gene dosage on chromosome 11 in children suffering from Beckwith-Wiedemann syndrome

  • Medical Genetics
  • Published:
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Abstract

The Beckwith-Wiedemann syndrome (BWS) is composed of multiple congenital malformations coupled with a high concurrent risk for the development of specific rare childhood tumours. The syndrome is characterised by a complex mode of inheritance, but recent evidence indicates that it is an autosomal dominant trait with variable penetrance. It has been previously suggested that major rearrangements of the short arm of chromosome 11 are involved in the aetiology of the disease. We undertook to search for rearrangements in 11p in four patients with BWS and their parents and siblings. By using cloned DNA fragments homologous to four genes located on 11p, namely catalase, parathyroid hormone, insulinlike growth factor II and the proto-oncogene c-Ha-Ras, we subjected DNA from the patients to a restriction fragment length polymorphism (RFLP) analysis after digestion with restriction enzymes. We found no evidence for any large scale deletions or amplifications in this chromosomal region. We therefore conclude that altered gene dosage is not, as has been suggested, a requirement for the development of BWS. This raises the question of whether some other molecular mechanism is responsible for the malformations observed.

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Abbreviations

BWS:

Beckwith-Wiedemann syndrome

IGFII:

insulin like growth factor II

RFLP:

restriction fragment length polymorphism

SSC:

0.15 M sodium chloride, 0.015 M sodium citrate

WAGR:

Wilms/aniridia/genitourinary abnormality syndrome

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Authors and Affiliations

  1. C.R.C. Developmental Tumours Research Group, Department of Zoology, University of Oxford, South Parks Road, OX1 3PS, Oxford, UK

    P. N. Schofield & W. Engström

  2. Department of Pediatric Surgery, Karolinska Institutet, St. Gorans Hospital, S-10401, Stockholm, Sweden

    S. Lindham

  3. Centre for Biotechnology, Karolinska Institutet, Huddinge Hospital, S-14186, Huddinge, Sweden

    W. Engström

Authors
  1. P. N. Schofield
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  2. S. Lindham
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  3. W. Engström
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Schofield, P.N., Lindham, S. & Engström, W. Analysis of gene dosage on chromosome 11 in children suffering from Beckwith-Wiedemann syndrome. Eur J Pediatr 148, 320–324 (1989). https://doi.org/10.1007/BF00444124

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  • DOI: https://doi.org/10.1007/BF00444124

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