title: Hereditary angioedema in a Jordanian family with a novel missense mutation in the C1-inhibitor N-terminal domain.
abstract: Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease caused by mutations in the SERPING1 gene. A Jordanian family, including 14 individuals with C1-INH-HAE clinical symptoms, was studied. In the propositus and his parents, SERPING1 had four mutations leading to amino acid substitutions. Two are known polymorphic variants (c.167T>C; p.Val34Ala and c.1438G>A; p.Val458Met), the others are newly described. One (c.203C>T; p.Thr46Ile) is located in the N-terminal domain of the C1-inhibitor protein and segregates with angioedema symptoms in the family. The other (c.800C>T; p.Ala245Val) belongs to the serpin domain, and derives from the unaffected father. DNA from additional 24 family members were screened for c.203C>T mutation in the target gene. All individuals heterozygous for the c.203C>T mutation had antigenic and functional plasma levels of C1-inhibitor below 50% of normal, confirming the diagnosis of type I C1-INH-HAE. Angioedema symptoms were present in 14 of 16 subjects carrier for the c.203T allele. Among these subjects, those carrying the c.800T variation had more severe and frequent symptoms than subjects without this mutation. This family-based study provides the first evidence that multiple amino acid substitutions in SERPING1 could influence C1-INH-HAE phenotype.
authors.affiliation: Princess Haya Biotechnology Center, Jordan University of Science and Technology, Irbid 22110, Jordan. Electronic address: sjaradat@just.edu.jo.
authors.forename: Saied A
authors.initials: SA
authors.lastname: Jaradat
authors.affiliation: "L. Sacco" Department of Biomedical and Clinical Sciences, University of Milan, Milan 20133, Italy. Electronic address: sonia.caccia@unimi.it.
authors.forename: Sonia
authors.initials: S
authors.lastname: Caccia
authors.affiliation: Princess Haya Biotechnology Center, Jordan University of Science and Technology, Irbid 22110, Jordan. Electronic address: Rifaatrr@yahoo.com.
authors.forename: Rifaat
authors.initials: R
authors.lastname: Rawashdeh
authors.affiliation: Princess Haya Biotechnology Center, Jordan University of Science and Technology, Irbid 22110, Jordan. Electronic address: motasemmelhem@yahoo.com.
authors.forename: Motasem
authors.initials: M
authors.lastname: Melhem
authors.affiliation: Pediatric Department, King Hussein Medical Center, Amman 11855, Jordan. Electronic address: hawamdeh56@yahoo.com.
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Hawamdeh
authors.affiliation: "L. Sacco" Department of Biomedical and Clinical Sciences, University of Milan, Milan 20133, Italy. Electronic address: thomas.carzaniga@unimi.it.
authors.forename: Thomas
authors.initials: T
authors.lastname: Carzaniga
authors.affiliation: Princess Haya Biotechnology Center, Jordan University of Science and Technology, Irbid 22110, Jordan. Electronic address: hazem_haddad1981@yahoo.com.
authors.forename: Hazem
authors.initials: H
authors.lastname: Haddad
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D003174:Complement C1 Inactivator Proteins / Q000235:genetics*; D050718:Complement C1 Inhibitor Protein; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D056829:Hereditary Angioedema Types I and II / Q000235:genetics*; D006801:Humans; D007597:Jordan; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human
keywords: C1-inhibitor; Hereditary angioedema; Jordan; N-terminal domain; SERPING1 gene