MOLECULAR-GENETIC ANALYSIS OF X-LINKED HYPOGAMMAGLOBULINEMIA AND ISOLATED GROWTH-HORMONE DEFICIENCY

In 1980 the clinical syndrome of X-linked hypogammaglobulinemia and is olated growth hormone deficiency (XLA/GHD) was described. XLA/GHD pati ents have reduced serum levels of Ig and normal cell-mediated immunity , and thus resemble patients with Bruton's X-linked agammaglobulinemia (XLA). However, XLA/GHD patients also have isolated GHD. Mutations an d deletions in the Bruton's tyrosine kinase gene (BTK) are responsible for Bruton's XLA. We investigated BTK gene expression in an XLA/GHD p atient from the family originally described by Northern analysis, cDNA sequencing, and Western analysis of protein production using mAb to B TK. BTK mRNA was normal in size and abundance, and the mRNA sequence w as normal over the coding region, except for a single silent mutation. BTK protein was present in normal amounts in PBMC of this patient. Th us, at the molecular level, XLA/GHD is a different disease entity from Bruton's XLA. These results suggest that undescribed genes critical f or B cell development and growth hormone production exist on the X chr omosome.