Ak. Gedeon et al., REFINEMENT OF THE BACKGROUND GENETIC-MAP OF XQ26-Q27 AND GENE LOCALIZATION FOR BORJESON-FORSSMAN-LEHMANN SYNDROME, American journal of medical genetics, 64(1), 1996, pp. 63-68
A detailed map of genetic markers was constructed around the gene for
the X-linked mental retardation syndrome of Borjeson-Forssman-Lehmann
(BFLS). A multipoint linkage map of framework markers across Xq26-27,
based on CEPH families, was integrated with the physical map, based on
a YAC contig, to confirm marker order. The remaining genetic markers,
which could not be ordered by linkage, were added to create the compr
ehensive genetic background map, in the order determined by physical m
apping, to determine genetic distances between adjacent markers, This
background genetic map is applicable to the refinement of the regional
localisation for any disease gene mapping to this region. The BFLS ge
ne was localised using this background map in an extended version of t
he family described by Turner et al. [1989]. The regional localisation
for BFLS extends between recombination events at DXS425 and DXS105, a
n interval of 24.6 cM on the background genetic map, The phenotypic fi
ndings commonly seen in the feet of affected males and obligate carrie
r females may represent a useful clinical indicator of carrier status
in potential female carriers in the family, Recombination between DXS4
25 and DXS105 in a female with such characteristic feet suggests that
the distal limit of the regional localisation for the BFLS gene might
reasonably be reduced to DXS294 for the purpose of selecting candidate
genes, reducing the interval for the BFLS gene to 15.5 cM. Positional
candidate genes from the interval between DXS425 and DXS105 include t
he SOX3 gene, mapped between DXS51(52A) and DXS98(4D-8). SOX3 may have
a role in regulating the development of the nervous system. The HMG-b
ox region of this single exon gene was examined by PCR for a deletion
and then sequenced. No deviation from normal was observed, excluding m
utations in the conserved HMG-box region as the cause of BFLS in this
family. (C) 1996 Wiley-Liss, Inc.