title: Intron-size constraint as a mutational mechanism in Rothmund-Thomson syndrome.
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.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Wang
authors.forename: Kim
authors.initials: K
authors.lastname: Worley
authors.forename: Anu
authors.initials: A
authors.lastname: Gannavarapu
authors.forename: Murali M
authors.initials: MM
authors.lastname: Chintagumpala
authors.forename: Moise L
authors.initials: ML
authors.lastname: Levy
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Plon
mesh_terms: D016475:3T3 Cells; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D012326:RNA Splicing; D053484:RecQ Helicases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011038:Rothmund-Thomson Syndrome / Q000201:enzymology / Q000235:genetics*; D014162:Transfection
chemical_list: D004247:DNA; D000251:Adenosine Triphosphatases; C506731:RECQL4 protein, human; D004265:DNA Helicases; D053484:RecQ Helicases