Genetic heterogeneity in X-linked agammaglobulinemia complicates carrier detection and prenatal diagnosis.
X-linked agammaglobulinemia (XLA) is a severe antibody deficiency disease reflecting an arrest of B lymphocyte differentiation at the level of precursor B cells. The disease is inherited in an X-linked recessive mode. In a single eight-generation pedigree the XLA gene was mapped to the Xq21.3-Xq22 area of the X chromosome. The data establish close linkage of the XLA locus to the DXS17 restriction fragment length polymorphic (RFLP) marker locus (the lod score exceeding 6 at phi = 0). A series of RFLP markers around the DXS17 locus provided an RFLP haplotype of use in genetic counselling within this pedigree. In one other pedigree a phenotypically identical disease was inherited but was accompanied by a high frequency of recombination with the DXS17 locus, which made localisation of the gene at the DXS17 locus highly unlikely (lod score less than -3). This genetic heterogeneity complicates genetic counselling within particular pedigrees, especially when the localization of the XLA gene involved in those pedigrees has not been established.
D000361:Agammaglobulinemia / Q000175:diagnosis / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D011296:Prenatal Diagnosis; D014960:X Chromosome
D005819:Genetic Markers