Intron-Size Constraint as a Mutational Mechanism in Rothmund-Thomson Syndrome

AUTOR(ES)

Wang, Lisa L.

FONTE

The American Society of Human Genetics

RESUMO

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 ∼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.

Documentos Relacionados

• Rothmund-Thomson syndrome associated with trisomy 8 mosaicism.
• Instability of lymphocyte chromosomes in a girl with Rothmund-Thomson syndrome.
• Rare presentation of Rothmund-Thomson syndrome with novel compound heterozygous mutations of the RECQL4 gene,
• Síndrome de Rothmund-Thomson e achados da superfície ocular: casos clínicos e revisão da literatura
• Rothmund-Thomson syndrome: two case reports show heterogeneous cutaneous abnormalities, an association with genetically programmed ageing changes, and increased chromosomal radiosensitivity.