X-linked phosphorylase kinase (PHK) deficiency causes X-linked liver g
lycogenosis (XLG) which is the most frequent fiver glycogen storage di
sorder in man. Recently we assigned XLG to the Xp22 chromosomal region
by linkage analysis in two families segregating XLG. In this study a
further localization of XLG in Xp22 was performed by extending the num
ber of Xp22 markers, by extension of the number of family members from
the two families of our previous study and by linkage analysis in fou
r additional XLG families. Two-point linkage analysis revealed lod sco
res of 4.60, 5.73, 5.28, 8.62 and 5.14 for linkage between XLG and the
DNA markers pXUT23 and pSE3.2-L(DXS16), pD2(DXS43), pTS247(DXS197) an
d pPA4B(DXS207), respectively, atl at 0% recombination. Linkage hetero
geneity was not observed in this set of families. Multipoint linkage a
nalysis increased the lod score for linkage between XLG and Xp22 to 16
.79 relative to DXS197/DXS207. The position of the XLG gene was confir
med by analysis of recombinational events locating the XLG gene betwee
n DXS85 and DXS41. The XLG gene could not be mapped more precisely in
this chromosomal region of approximately 20cM because of the absence o
f recombinational events between the XLG gene and the Xp22 markers. As
we have previously shown that the rabbit liver alpha subunit of PHK (
PHKA2) hybridizes to human Xp22, we isolated a human PHKA2 cDNA from a
human hepatoma lambda gt11 cDNA library. Fluorescent in situ hybridiz
ation mapped human PHKA2 to Xp22. As this physical mapping coincidies
with the genetic mapping of XLG by linkage analysis, PHKA2 most probab
ly harbours the mutation(s) responsible for XLG.