Hereditary angioedema: the mutation spectrum of SERPING1/C1NH in a large Spanish cohort
Identificadores
URI: http://hdl.handle.net/20.500.12020/1141ISSN: 1059-7794
DOI: https://doi.org/10.1002/humu.20197
Autor/es
Roche, Olga; Blanch, Álvaro; Duponchel, Christiane; Fontán, Gumersindo; Tosi, Mario; [et al.]Fecha
2005Tipo de documento
articleMateria/s Unesco
24 Ciencias de la VidaResumen
Hereditary angioedema (HAE) is a disease caused by defects in the C1 inhibitor gene (SERPING1/C1NH). We
screened the entire C1NH gene for mutations in a large series of 87 Spanish families (77 with type I, and 10
with type II HAE) by SSCP, sequencing, Southern blotting, and quantitative multiplex PCR of short fluorescent
fragments (QMPSF), and we characterized several defects at the mRNA level. We found large rearrangements
in 13 families, and point mutations or microdeletions/insertions in 74 families. The 13 large rearrangements
included nine exon deletions, of which at least eight were distinct, two were distinct exon duplications, and two
were rearrangements whose precise nature could not be determined. We confirmed that exon 4 is particularly
prone to rearrangements. Thirty-six mutations were unreported, and included 10 microdeletions/insertions, 10
missense, five nonsense, eight splicing, and three splicing or missense mutations. Moreover, we detected six
novel uncharacterized sequence variants (USV). RT-PCR studies showed that in addition to several intronic
splice site mutations tested, the exonic mutations c.882C4G and c.884T4G, located near the 30 end of exon 5,
also produced exon skipping. This is the first evidence of SERPING1/C1NH mutations in coding regions that
differ from the canonical splice sites that affect splicing, which suggests the presence of an exonic splicing
enhancer (ESE) in exon 5.