Physical fine mapping of genes underlying X-linked deafness and non fra(X)-X-linked mental retardation at Xq21

Abstract

Linkage studies and cytogenetically visible deletions associated with nonspecific X-linked mental retardation (XLMR) and a specific form of deafness (DFN3) have indicated that the genes responsible for these disorders are located at Xq21. Using DNA probes from this region, we have studied several overlapping deletions spanning different parts of Xq21. This has enabled us to assign the DFN3 gene and a gene for nonspecific XLMR to an interval that encompasses the locus DXS232 and that is flanked by DXS26 and DXS121.

Yeast Artificial Chromosome Cloning of the Xq13.3-q21.31 Region and Fine Mapping of a Deletion Associated with Choroideremia and Nonspecific Mental Retardation

“…Together, these data letions in the X q 2 1 region are associated with strongly suggest that a locus for XLM R is situ-DFN3, MR and CHM [2,6,7,26,27]. The ated in the chromosomal region defined by identification of submicroscopic deletions as-intervals 8, 9 and 10.…”

“…;[31][32][33][34][35], In view o f and im m ature behavior and possibly mild the large number of deletions known in Xq21, learning deficits [36]. Since the deletion in it is striking that thus far no small deletions patient TD is close to the M R locus [7], it have been found with nonspecific mental re-could affect the proper transcription o f the tardation or with a combination of M R with M R gene. This might explain the complex either DFN3 or CHM.…”

“…These deletions often give rise to con tiguous gene syndromes including choroider emia (CHM), X-linked deafness (DFN3) and nonspecific mental retardation (MR) [3][4][5][6][7]. Sizeable deletions have also been found in patients with nonsyndromic CHM or DFN3 [4-6, 8,9], Employing positional cloning strategies, the genes underlying CHM and DFN3 have been isolated.…”

“…Sizeable deletions have also been found in patients with nonsyndromic CHM or DFN3 [4-6, 8,9], Employing positional cloning strategies, the genes underlying CHM and DFN3 have been isolated. Analysis of patients with Xq21 deletions and syndromic and nonsyndromic forms of MR has enabled us to map the gene for X-linked MR to a region between CHM and DFN3 [4,7,[10][11][12][13].…”

Regulation of striatal D1A dopamine receptor gene transcription by Brn-4.

“…Non-specific bands are indicated by NS. periment showed supershifted complexes of striatal Brn-4 with PRE1 or PRE2 (Fig. 5J) (44,45). Thus, careful neurologic and psychologic evaluations of those patients are important, since knock-out of the DiA dopamine receptor gene causes only functional changes rather than neuronal death or gross morphological anomalies in the nervous system (46,47 …”