A novel splice site mutation in the SERPING1 gene leads to haploinsufficiency by complete degradation of the mutant allele mRNA in a case of familial hereditary angioedema.
Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) is a rare autosomal-dominant and life-threatening disorder caused by mutations in SERPING1 gene. It is characterized by attacks of angioedema involving the skin and/or the mucosa of the upper airways, as well as the intestinal mucosa. Here we report the case of a patient with HAE-C1INH without family history of angioedema. By sequencing the SERPING1 gene we detected a novel mutation (c.1249 + 5G > A) affecting the 5' donor splice site in intron 7. We analyzed the SERPING1 cDNA expecting a defect in splicing process but only the wild type allele was detected. SNP analysis of the cDNA sequence demonstrated that only one of the two alleles was present, indicating that the mRNA from the mutated allele was completely degraded. This study reinforces the concept of incomplete penetrance of this disorder since the patients' mother never presented any sign of angioedema despite carrying the same mutation.
Immunology Division, Vall d'Hebron Research Institute (VHIR), Hospital Universitari Vall d'Hebron (HUVH), Barcelon, Spain.
Roger
R
Colobran
Ricardo
R
Pujol-Borrell
Manuel
M
Hernández-González
Mar
M
Guilarte
D000328:Adult; D000483:Alleles; D054179:Angioedemas, Hereditary / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D003174:Complement C1 Inactivator Proteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D050718:Complement C1 Inhibitor Protein; D005260:Female; D057895:Haploinsufficiency; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009154:Mutation; D019683:Penetrance; D022821:RNA Splice Sites; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D022821:RNA Splice Sites; D012333:RNA, Messenger; C469952:SERPING1 protein, human