Mapping of a gene (MRXS9) for X-linked mental Retardation, microcephaly, and variably short stature to Xq12-q21.31

Three boys from two families were identified as having a syndrome of X-link ed mental retardation (XLMR) with microcephaly and short stature, clinicall y resembling Renpenning syndrome but with normal size of testicles in affec ted men. When the effort to map the gene for the above condition was initia ted, it was realized that the two families were actually related to each ot her. Over 50 polymorphic markers of known locations along the X chromosome were scored in this family in a study to map the disease gene. Nine affecte d and four unaffected males were genotyped to produce a maximum LOD score o f 4.42 at zero recombination with markers in proximal Xq, The results indic ate that the gene responsible for this disorder is located in the cytogenet ic Xq12 to Xq21.31 interval of the X chromosome within a section of chromos ome of about 17 cM between the AR and DXS1217 loci over some 25 mb. Since t he gene for the X-linked mental retardation from the original Saskatchewan family described by Renpenning [Renpenning et al,, 1962: Can Med Assoc J 87 :954-956; Fox and Gerrard, 1980: Am J Med Genet 7:491-495] was recently map ped to a different nonoverlapping region [Stevenson et al,, 1998: Am J Hum Genet 62:1092-1101] this would appear to be a separate disorder. (C) 1999 W iley-Liss, Inc.