Intron-Size Constraint as a Mutational Mechanism in Rothmund-Thomson Syndrome
Open Access
- 1 July 2002
- journal article
- Published by Elsevier BV in American Journal of Human Genetics
- Vol. 71 (1), 165-167
- https://doi.org/10.1086/341234
Abstract
Rothmund-Thomson syndrome (RTS) is an autosomal recessive disorder caused by deleterious mutations in the RECQL4 gene on chromosome 8. The RECQL4 gene structure is unusual because it contains many small introns <100 bp. We describe a proband with RTS who has a novel 11-bp intronic deletion, and we show that this mutation results in a 66-bp intron too small for proper splicing. Constraint on intron size may represent a general mutational mechanism, since human-genome analysis reveals that approximately 15% of genes have introns <100 bp and are therefore susceptible to size constraint. Thus, monitoring of intron size may allow detection of mutations missed by exon-by-exon approaches.Keywords
This publication has 12 references indexed in Scilit:
- Human Hypertension Caused by Mutations in WNK KinasesScience, 2001
- Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patientsAmerican Journal of Medical Genetics, 2001
- Characterization of the Effects of Mutations in the Putative Branchpoint Sequence of Intron 4 on the Splicing within the Human Lecithin:cholesterol Acyltransferase GeneJournal of Biological Chemistry, 2000
- Rothmund-Thomson syndrome due toRECQ4 helicase mutations: Report and clinical and molecular comparisons with Bloom syndrome and Werner syndromeAmerican Journal of Medical Genetics, 2000
- Rothmund–Thomson Syndrome Responsible Gene, RECQL4: Genomic Structure and ProductsGenomics, 1999
- Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndromeNature Genetics, 1999
- Splicing mutations of the polycystic kidney disease 1 (PKD1) gene induced by intronic deletionHuman Molecular Genetics, 1995
- Exon Recognition in Vertebrate SplicingJournal of Biological Chemistry, 1995
- Rothmund-Thomson syndrome: Review of the world literatureJournal of the American Academy of Dermatology, 1992
- mRNA precursor splicing in vivo: sequence requirements determined by deletion analysis of an intervening sequence.Proceedings of the National Academy of Sciences of the United States of America, 1985