Letter to the Editor

Refined Gene Localization for MRX8

To the Editor:

The gene for the X-linked mental retardation entity,MRX8, was initially localized to a broad region rangingfrom Xp11.3-q21.3 [Schwartz et al., 1992]. Linkage wasobserved at DXS3 with a LOD score of 2.71 at zerorecombination. The flanking loci were determined to beMAOA in Xp11.3 and DXS456 in Xq22.3. However, theLOD score of 2.44 was lower than the estimated maxi-mum LOD score of 3.44, which is possible if a marker isfully informative in this family. We have restudied thisfamily using numerous microsatellite markers in orderto refine the localization and make it compatible withthe newer genetic map of the X chromosome.

The new linkage data are presented in Table I. Maxi-mum LOD scores of 2.74 at the ARA locus and 1.83 atlocus DXS1111 in Xq12 were obtained. As no recombi-nation was detected between these two loci in the fam-

ily and as some women were fully informative for onebut not the other, a haplotype was created. Using thishaplotype in a two-point marker-to-disease analysis, amaximum LOD score of 3.04 was determined (Table I).The closest flanking loci were found to be DXS1003 inXp11.2 and DXS1166 in Xq13 (Table I). These resultsplace MRX8 in a narrower pericentric region of the Xchromosome than previously reported [Schwartz et al.,1992]. The newer localization interval is now 25 Mbrather than 65 Mb [Nelson et al., 1995]. This is yetanother instance in which restudy of an MRX entitypreviously localized to a broad pericentric region hasresulted in the location interval being narrowed to con-tain primarily the proximal portion of the short armand excluding much of the proximal long arm [Tackelset al., 1998]. Clearly it is of considerable value to re-study MRX entities that were mapped prior to avail-ability of highly informative microsatellite markers.

Contract grant sponsor: National Institute of Child Health andHuman Development; Contract grant number: 2RO1HD26202;Contract grant sponsor: South Carolina Department of Disabili-ties and Special Needs.

*Correspondence to: Charles E. Schwartz, Ph.D., J.C. Self Re-search Institute, One Gregor Mendel Circle, Greenwood, SC29646. E-mail: schwartz@ggc.org

Received 13 February 1998; Accepted 9 November 1998

TABLE I. Two-Point LOD Scores for X-Chromosome Loci and MRX8

Marker Location

Recombination

umax Zmax0.001 0.01 0.05 0.1 0.2 0.3 0.4

DXS1055 Xp11.2 −2.32 −1.32 −0.61 −0.3 0.00 0.12 0.10 0.347 0.12DXS1003 Xp11.2 −0.27 0.69 1.19 1.25 1.04 0.69 0.29 0.09 1.25DXS1039 Xp11.23 0.95 0.93 0.87 0.78 0.58 0.35 0.11 0.00 0.95DXS988 Xp11.2 1.53 1.51 1.4 1.26 0.94 0.59 0.22 0.00 1.53DXS991 Xp11.21 1.30 1.29 1.22 1.21 0.91 0.65 0.36 0.00 1.30ARA Xq12 2.73 2.70 2.53 2.31 1.82 1.24 0.59 0.00 2.74DXS1111 Xq12 1.83 1.80 1.68 1.51 1.15 0.74 0.29 0.00 1.83ARA/1111 Xq12 3.03 2.99 2.81 2.57 2.02 1.38 0.65 0.00 3.04DXS983 Xq12 1.83 1.80 1.68 1.51 1.15 0.74 0.29 0.00 1.83DXS1166 Xq13.2 0.03 1.00 1.53 1.61 1.42 1.01 0.47 0.09 1.61DXS566 Xq13.3 −0.27 0.70 1.24 1.34 1.19 0.84 0.39 0.10 1.34DXS995 Xq21.1 −11.26 −6.29 −2.94 −1.62 −0.51 −0.06 0.07 0.41 0.08DXS1002 Xq21.31 −4.07 −2.09 −0.78 −0.3 0.03 0.08 0.03 0.50 0.23DXS990 Xq21.33 0.03 0.99 1.48 1.52 1.26 0.85 0.36 0.08 1.53DXS101 Xq22.1 0.03 0.99 1.48 1.52 1.27 0.86 0.37 0.08 1.53DXS424 Xq23 −2.97 −1.01 0.21 0.59 0.70 0.53 0.25 0.17 0.71

American Journal of Medical Genetics 85:309–310 (1999)

© 1999 Wiley-Liss, Inc.

ACKNOWLEDGMENTS

This work was supported in part by a grant from theNational Institute of Child Health and Human Devel-opment (2RO1HD26202) to C.E.S. and a grant from theSouth Carolina Department of Disabilities and SpecialNeeds.

REFERENCESNelson DL, Ballabio A, Cremers F, Monaco AP, Schlessinger D. 1995. Re-

port of the sixth international workshop on X chromosome mapping.Cytogenet Cell Genet 71:308–342.

Schwartz CE, May M, Huang T, Ledbetter D, Anderson G, Barker DF,

Lubs HA, Arena JF, Stevenson RE. 1992. MRX8: an X-linked mentalretardation condition with linkage Xq21.3. Am J Med Genet 43:467–474.

Tackels D, Thibodeau S, Michels V, Schwartz CE. 1999. Gene localizationfor MRX7. Am J Med Genet 85:288–289.

Darci TackelsCharles E. Schwartz*Center for Molecular StudiesJ.C. Self Research Institute of Human

GeneticsGreenwood Genetic CenterGreenwood, South Carolina

310 Tackels and Schwartz