title: Congenital deficiency of factor XIII caused by two missense mutations in a Dutch family.
abstract: We present the clinical, biochemical and genomic findings of a family with congenital factor XIII (FXIII) deficiency. Congenital FXIII deficiency is a very rare autosomal recessive bleeding disorder, characterized by umbilical cord bleeding at birth and spontaneous intracranial haemorrhage. Routine clotting tests are normal, which may delay the diagnosis, leading to an increased chance of severe sequelae. The propositus and her brother, known with haemorrhagic diathesis, were found to be compound heterozygous with a known missense mutation (1050 G --> T transversion in exon 7, Val316Phe substitution) and a novel mutation 889 G --> A in exon 6, which predicts a Gly262Glu substitution. As these mutations were known in the family, DNA obtained from cord blood of the youngest sister was analysed for mutations in exons 6 and 7 only. We postulate that the diagnosis was facilitated by determining the two different mutations in the genotype of this family. The analysis showed that she was heterozygous for the exon 7 mutation. Hence, she was not at risk of experiencing haemorrhagic diathesis. This diagnosis avoided the administration of FXIII concentrate to the newborn.
authors.affiliation: Department of Paediatrics, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Onland
authors.forename: A N
authors.initials: AN
authors.lastname: Böing
authors.forename: A B
authors.initials: AB
authors.lastname: Meijer
authors.forename: M C L
authors.initials: MC
authors.lastname: Schaap
authors.forename: R
authors.initials: R
authors.lastname: Nieuwland
authors.forename: K
authors.initials: K
authors.lastname: Haasnoot
authors.forename: A
authors.initials: A
authors.lastname: Sturk
authors.forename: M
authors.initials: M
authors.lastname: Peters
mesh_terms: D000328:Adult; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005176:Factor XIII / Q000235:genetics*; D005177:Factor XIII Deficiency / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D014470:Umbilical Cord
chemical_list: D005176:Factor XIII