Intron-size constraint as a mutational mechanism in Rothmund-Thomson syndrome.

TitleIntron-size constraint as a mutational mechanism in Rothmund-Thomson syndrome.
Publication TypeJournal Article
Year of Publication2002
AuthorsWang, LL, Worley, K, Gannavarapu, A, Chintagumpala, MM, Levy, ML, Plon, SE
JournalAm J Hum Genet
Date Published2002 Jul
Keywords3T3 Cells, Adenosine Triphosphatases, Animals, Base Sequence, DNA, DNA Helicases, Humans, Introns, Mice, Molecular Sequence Data, Mutation, RecQ Helicases, Reverse Transcriptase Polymerase Chain Reaction, RNA Splicing, Rothmund-Thomson Syndrome, Transfection

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.

Alternate JournalAm J Hum Genet
PubMed ID12016592
PubMed Central IDPMC384974
Grant ListU54 HG003273 / HG / NHGRI NIH HHS / United States

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