title: Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases.
abstract: 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 characterized by short stature, radial ray defects and other malformations, as well as infantile diarrhoea, 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 bone development.
authors.affiliation: Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland.
authors.forename: H Annika
authors.initials: HA
authors.lastname: Siitonen
authors.forename: Outi
authors.initials: O
authors.lastname: Kopra
authors.forename: Helena
authors.initials: H
authors.lastname: Kääriäinen
authors.forename: Henna
authors.initials: H
authors.lastname: Haravuori
authors.forename: Robin M
authors.initials: RM
authors.lastname: Winter
authors.forename: Anna-Marja
authors.initials: AM
authors.lastname: Säämänen
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Marjo
authors.initials: M
authors.lastname: Kestilä
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001816:Bloom Syndrome / Q000235:genetics*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D053484:RecQ Helicases; D011038:Rothmund-Thomson Syndrome / Q000235:genetics*; D014898:Werner Syndrome / Q000235:genetics*
chemical_list: D000251:Adenosine Triphosphatases; C506731:RECQL4 protein, human; D004265:DNA Helicases; D053484:RecQ Helicases