Rothmund-Thomson Syndrome (RTS) is a rare autosomal recessive genodermatosis with a heterogeneous clinical profile. Mutations in RECQL4, encoding a RecQ DNA helicase, are present in a large fraction, but not all clinically diagnosed patients, allowing to classify RTS among the RecQ helicase chromosomal instability defects including Bloom's and Werner's syndromes. Results of RECQL4 test coupled to the variable clinical presentation favored the splitting of RTS clinical phenotype into nosological entities under distinct genetic control. In parallel, lumping of the RECQL4 gene to two other diseases, RAPADILINO and Baller-Gerold has paved the way to unravel through allelic heterogeneity complex genotype-phenotype correlations. Recql4 knockout mice provided crucial insights into the comprehension of the functional role of RECQL4 helicase, which have been corroborated by the initial biochemical characterization of RECQL4 protein and its acting pathway and by studies on RECQL4 homologs in yeast and Xenopus. A role for RECQL4 in initiation of DNA replication and in sister chromatid cohesion has been proposed, which currently fits the pieces of evidence achieved by different approaches. Further work is needed to define the specific and shared functions of RECQL4 in relation to other RecQ helicases and to connect RECQL4 diseases to other genomic instability syndromes with birth defects and cancer predisposition

Rothmund-Thomson syndrome and RECQL4 defect : splitting and lumping / L. Larizza, I. Magnani, G. Roversi. - In: CANCER LETTERS. - ISSN 0304-3835. - 232:1(2006 Jan 28), pp. 107-120.

Rothmund-Thomson syndrome and RECQL4 defect : splitting and lumping

L. Larizza
Primo
;
I. Magnani
Secondo
;
G. Roversi
Ultimo
2006

Abstract

Rothmund-Thomson Syndrome (RTS) is a rare autosomal recessive genodermatosis with a heterogeneous clinical profile. Mutations in RECQL4, encoding a RecQ DNA helicase, are present in a large fraction, but not all clinically diagnosed patients, allowing to classify RTS among the RecQ helicase chromosomal instability defects including Bloom's and Werner's syndromes. Results of RECQL4 test coupled to the variable clinical presentation favored the splitting of RTS clinical phenotype into nosological entities under distinct genetic control. In parallel, lumping of the RECQL4 gene to two other diseases, RAPADILINO and Baller-Gerold has paved the way to unravel through allelic heterogeneity complex genotype-phenotype correlations. Recql4 knockout mice provided crucial insights into the comprehension of the functional role of RECQL4 helicase, which have been corroborated by the initial biochemical characterization of RECQL4 protein and its acting pathway and by studies on RECQL4 homologs in yeast and Xenopus. A role for RECQL4 in initiation of DNA replication and in sister chromatid cohesion has been proposed, which currently fits the pieces of evidence achieved by different approaches. Further work is needed to define the specific and shared functions of RECQL4 in relation to other RecQ helicases and to connect RECQL4 diseases to other genomic instability syndromes with birth defects and cancer predisposition
Rothmund–Thomson syndrome ; RECQL4 helicase ; Locus and allelic heterogeneity ; Osteosarcoma ; Chromosomal instability ; Defective sister chromatid cohesion ; Defective replication initiation
Settore MED/03 - Genetica Medica
28-gen-2006
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/61779
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