Paternal mosaicism and hereditary angioedema in a Taiwanese family

• Published in: Annals of allergy, asthma, & immunology Vol. 99; no. 4; p. 375
• Main Authors: Yu, Tai-Chang, Shyur, Shyh-Dar, Huang, Li-Hsin, Wen, Da-Chin, Li, Jia-Shiuan
• Format: Journal Article
• Language: English
• Published: United States 01.10.2007
• Subjects: Adult; Alleles; Amino Acid Sequence; Angioedema - blood; Angioedema - genetics; Complement C1 Inactivator Proteins - genetics; Complement C1 Inhibitor Protein; Complement C3 - analysis; Complement C4 - analysis; DNA Mutational Analysis; Exons - genetics; Family Health; Female; Frameshift Mutation; Genetic Diseases, Inborn - blood; Genetic Diseases, Inborn - genetics; Humans; Male; Molecular Sequence Data; Mosaicism; Parents; Pedigree; Sequence Deletion; Serpins - blood; Serpins - genetics; Taiwan
• ISSN: 1081-1206
• DOI: 10.1016/S1081-1206(10)60557-1

Hereditary angioedema (HAE) is a rare disorder characterized by recurrent attacks of localized subcutaneous or submucosal edema. It is inherited in an autosomal dominant fashion and caused by a deficiency of C1 inhibitor (C1 INH). Most patients with HAE have an absolute deficiency of C1 INH (type I HAE), whereas the rest (approximately 15%) synthesize a dysfunctional C1 INH protein (type II HAE). Mosaicism is rare in HAE. To describe the clinical manifestations, laboratory findings, and molecular genetic studies in a Taiwanese family with type I HAE with paternal mosaicism. A family that included a 34-year-old man (index patient) and his 25-year-old brother who both had recurrent peripheral angioedema was evaluated. A younger sister had died of an unexplained cause at 18 years of age. We analyzed blood levels of C3, C4, and C1 INH and sequenced the SERPING] (C1NH) gene that codes for C1 INH in 5 family members, including the parents and 3 brothers. The 4 men in the family had a novel mutation c.3_73del, p.N1fsX34 in exon 3 of the C1INH gene, resulting in C1 INH deficiency. Although the father carried this mutant gene, he had normal serum levels of C1 INH. Based on quantitative analysis of allele dosage by DNA fragment analysis (GeneScan), the father was determined to have genetic mosaicism. Parental mosaicism is a possible explanation for normal C1 INH plasma concentrations in both parents despite clinically apparent HAE in the children.