title: Twin carriers of X-linked agammaglobulinemia (XLA) due to germline mutation in the Btk gene.
abstract: We report on an X-linked agammaglobulinemia (XLA) family in which mothers of two affected cousins were monozygotic twins. We analyzed the Btk gene of several members in three generations of the family by SSCP analysis, DNA sequencing, and RFLP analysis following polymerase chain reaction-amplification of the individual exons. We identified a missense point mutation, G1817C (R562P), in exon 17 of the Btk gene in the affected cousins. The same mutation was also present in both mothers (twin sisters) of the cousins identifying them as carriers. However, the mutation was absent in all other relatives including the grandmother of the cousins (mother of the twin sisters). This strongly suggests that the mutation in the Btk gene had originated in one of the germ lines or in the zygote. This may be the first demonstration of a germ line (or zygotic) mutation in XLA.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Altanta, Georgia, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Curtis
authors.forename: M D
authors.initials: MD
authors.lastname: Hebert
authors.forename: B K
authors.initials: BK
authors.lastname: Saha
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D014430:Twins, Monozygotic; D014960:X Chromosome
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human