Chromosomal jumping from the DXS165 locus allows molecular characterization of four microdeletions and a de novo chromosome X/13 translocation associated with choroideremia.

Abstract

Choroideremia (tapeto-choroidal dystrophy, TCD), an X chromosome-linked disorder ofretina and choroid, causes progressive nightblindness and central blindness in affected males by the third to fourth decade of life. Recently, we have been able to map the TCD gene to a small region of overlap between five different, male-viable Xq21 deletions that were found in patients with TCD and other clinical features. Two families were identified in which classical, nonsyndromic TCD is associated with small interstitial deletions that are only detectable with probe plbD5 (DXS165). To characterize these and two other deletions that were identified more recently, we have used the chromosome walking and jumping techniques to generate a set of five chromosomal-jumping clones flanking the DXS165 locus at various distances. With these clones, we could localize four of the eight deletion endpoints and the breakpoint on the X chromosome of a female with a de novo X/13 translocation and choroideremia. These studies assign the TCD gene, or part of it, to a DNA segment of only 15-20 kilobases.

Molecular and cytogenetic studies of an X;autosome translocation in a patient with premature ovarian failure and review of the literature

“…The breakpoint in the POF patient was at Xq21.3, with DXS72 proximal to the breakpoint; this locus is distal to the breakpoint in our patient. A female with choroideremia and POF has been reported with a balanced t(X;A): 46,X,t(X;13)(q21.2;pl2) which is also distal to the breakpoint in our patient (distal to DXS72) [Siu et al, 1990;Cremers et al, 1989;Merry et al, 19921. Somatic cell hybrids were generated from cell lines of five women with t(XA) and "troubles of ovarian function" [Philippe et al, 19911.…”

“…Two patients with choroideremia, t(XA) and ovarian dysfunction have been reported. The patient described by Siu et al [1990] has mild choroideremia and POF; based on molecular studies the translocation is within the choroideremia gene [Cremers et al, 1989;Merry et al, 19921. Another woman has been reported with choroideremia and ovarian dysgenesis manifesting as primary amenorrhea with a 46,X,t(X,7)(qZl.2;pl4) karyotype [Kaplan et al, 19891. We are not aware of molecular studies in this patient to rule out a deletion associated with the translocation, leading to a contiguous gene syndrome.…”

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.…”

Choroideremia: linkage analysis with physically mapped close DNA-markers

“…Moreover, the DXS165 locus was found to detect chromosomal microdeletions in two males with choroideremia and no other symptoms (Cremers et al 1987). DNA clones generated by chromosomal walking and jumping from the DXS165 locus (Cremers et al 1989b), and preparative field inversion gel electrophoresis , flank the translocation breakpoint of a de novo X;13 translocation in a TCD female, and detect minideletions in 8 patients with classical choroideremia (Cremers et al 1989b. Thus, the location of TCD is already physically defined.…”

“…The summary of the order and orientation of these loci as established by physical mapping is Xcen-DXS367-DXS233-DXS165-pZll-DXS95-DXYS1-DXYS69-Xtel (Cremers et al 1989a(Cremers et al , 1989bMerry et al 1989Merry et al , 1990D.Page, personal communication).…”