» Articles » PMID: 15971231

Hereditary Angioedema: the Mutation Spectrum of SERPING1/C1NH in a Large Spanish Cohort

Overview
Journal Hum Mutat
Specialty Genetics
Date 2005 Jun 23
PMID 15971231
Citations 24
Authors
Affiliations
Soon will be listed here.
Abstract

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.882C>G and c.884T>G, located near the 3' 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.

Citing Articles

Hereditary Angioedema with Normal C1 Inhibitor: an Updated International Consensus Paper on Diagnosis, Pathophysiology, and Treatment.

Zuraw B, Bork K, Bouillet L, Christiansen S, Farkas H, Germenis A Clin Rev Allergy Immunol. 2025; 68(1):24.

PMID: 40053270 PMC: 11889046. DOI: 10.1007/s12016-025-09027-4.


Molecular assessment of splicing variants in a cohort of patients with inborn errors of immunity: methodological approach and interpretation remarks.

Miguel Berenguel L, Gianelli C, Matas Perez E, Del Rosal T, Mendez Echevarria A, Robles Marhuenda A Front Immunol. 2025; 15:1499415.

PMID: 39944559 PMC: 11814461. DOI: 10.3389/fimmu.2024.1499415.


Complex analysis of the national Hereditary angioedema cohort in Slovakia - Identification of 12 novel variants in gene.

Markocsy A, Hrubiskova K, Hrubisko M, Freiberger T, Grombirikova H, Dolesova L World Allergy Organ J. 2024; 17(3):100885.

PMID: 38486718 PMC: 10937951. DOI: 10.1016/j.waojou.2024.100885.


Functional Characterization of Two Novel Intron 4 Gene Splice Site Pathogenic Variants in Families with Hereditary Angioedema.

Shchagina O, Gracheva E, Chukhrova A, Bliznets E, Bychkov I, Kutsev S Biomedicines. 2024; 12(1).

PMID: 38255179 PMC: 10813231. DOI: 10.3390/biomedicines12010072.


Application of a dried blood spot based proteomic and genetic assay for diagnosing hereditary angioedema.

Iurascu M, Balla Z, Pereira C, Andrasi N, Varga L, Csuka D Clin Transl Allergy. 2023; 13(11):e12317.

PMID: 38006386 PMC: 10668000. DOI: 10.1002/clt2.12317.