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Genetic heterogeneity in X‐linked agammaglobulinemia complicates carrier detection and prenatal diagnosis
Author(s) -
Mensink E. J. B. M.,
Thompson A.,
Schot J. D. L.,
Kraakman M. E. M.,
Sandkuyl L. A.,
Schuurman R. K. B.
Publication year - 1987
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1987.tb02775.x
Subject(s) - locus (genetics) , genetics , x linked agammaglobulinemia , pedigree chart , restriction fragment length polymorphism , biology , genetic linkage , haplotype , x chromosome , gene mapping , genetic marker , genetic counseling , gene , genetic heterogeneity , genotype , chromosome , signal transduction , tyrosine kinase , phenotype , bruton's tyrosine kinase
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 lodscore exceeding 6 at = 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 < –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.