Human Molecular Genetics Advance Access published online on September 2, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddg306
© 2003 by Oxford University Press
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1 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
* To whom correspondence should be addressed. E-mail: marjo.kestila{at}ktl.fi.
The RECQL4 helicase gene is a member of the RECQL gene family, mutated in some Rothmund-Thomson syndrome (RTS) patients. Other members of this gene family are BLM mutated in Bloom syndrome, WRN mutated in Werner syndrome and RECQL and RECQL5. All polypeptides encoded by RECQL genes share a central region of seven helicase domains. The function of RECQL4 remains unknown, but based on the domain homology it possesses ATP-dependent DNA helicase activity such as BLM and WRN. Rothmund-Thomson, Bloom and Werner syndromes have overlapping clinical features, of which high predisposition to malignancies is the most remarkable feature. Here we report a fourth syndrome resulting in mutations in the RECQL genes. RAPADILINO syndrome is an autosomal recessive disorder characterised by short stature, radial ray defects and other malformations, as well as infantile diarrhea, but not by a significant cancer risk. Four mutations in the RECQL4 gene were found in the Finnish patients, the most common mutation representing exon 7 in-frame deletion saving the helicase domain and showing dominant effect over other three nonsense mutations. The tissue expression of Recql4 in mouse well agrees with the tissue symptoms of RAPADILINO. The skeletal malformations in RAPADILINO and RTS patients as well as the high osteosarcoma risk in RTS propose a special role for RECQL4 in the bone development.
Article
MOLECULAR DEFECT OF THE RAPADILINO SYNDROME EXPANDS THE PHENOTYPE SPECTRUM OF RECQL DISEASES
2 Department of Medical Genetics, The Family Federation of Finland, Helsinki, Finland; Department of Medical Genetics, University of Turku, Turku, Finland; Department of Paediatrics, Turku University Central Hospital, Turku, Finland
3 Department of Clinical and Molecular Genetics, Institute of Child Health, London, UK
4 Department of Medical Biochemistry and Molecular Biology, University of Turku, Turku, Finland
5 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland; Department of Medical Genetics, University of Helsinki, Helsinki, Finland
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