title: Congenital factor XIII deficiency caused by two mutations in eight Tunisian families: molecular confirmation of a founder effect.
abstract: Inherited factor XIII (FXIII) deficiency is a rare bleeding disorder characterized by an umbilical bleeding during the neonatal period, delayed soft tissue bruising, mucosal bleeding spontaneous intracranial hemorrhage, and soft tissue hemorrhages. Congenital FXIII deficiency is an autosomal recessive disorder, usually attributed to a defect in the FXIIIA and B subunits coding, respectively, by F13A and F13B genes. The aim of this study was to determine the molecular defects responsible for congenital factor XIII deficiency in eight Tunisian families. Molecular analysis was performed by direct DNA sequencing of polymerase chain reaction amplified fragments spanning the coding regions and splice junctions of the FXIIIA subunit gene (F13A) in probands and in families' members and compared with the reported sequence of this gene. In all patients, FXIIIA activity was undetectable and the FXIIIB was within the normal range. Direct sequencing of the F13A gene in all probands showed two mutations: the c.869insC mutation found in eight patients and the c.1226G > A transition found in only one. We also confirmed the presence of a founder effect for the first frequent mutation by using two microsatellite markers, HUMF13A01 and a generated ployAC marker (HUMF13A02). We describe here molecular abnormalities found in nine Tunisian probands diagnosed with FXIIIA deficiency. The identification of the founder mutation and polymorphisms allowed a genetic counseling in relatives of these families, and the antenatal diagnosis is now available.
authors: Human Molecular Genetic Laboratory, Faculty of Medicine of Sfax, Avenue Magida Boulila, 3029 Sfax, Tunisia. nacim.louhichi@gmail.com
authors: Nacim
authors: N
authors: Louhichi
authors: Moez
authors: M
authors: Medhaffar
authors: Ikhlass
authors: I
authors: Hadjsalem
authors: Emna
authors: E
authors: Mkaouar-Rebai
authors: Nourhene
authors: N
authors: Fendri-Kriaa
authors: Houda
authors: H
authors: Kanoun
authors: Firas
authors: F
authors: Yaïch
authors: Tawfik
authors: T
authors: Souissi
authors: Moez
authors: M
authors: Elloumi
authors: Faiza
authors: F
authors: Fakhfakh
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D005176:Factor XIII / Q000235:genetics / Q000378:metabolism; D005177:Factor XIII Deficiency / Q000175:diagnosis / Q000235:genetics*; D026122:Factor XIIIa / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D016368:Frameshift Mutation / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D010375:Pedigree; D014416:Tunisia
chemical_list: D005176:Factor XIII; C054380:factor XIIIb; D026122:Factor XIIIa