(last modified October 29, 2001)
Female DMD patients have played a crucial role in the mapping and isolation of the DMD-gene. At a time when the localization of the DMD gene to Xp21 had not been firmly established, the identification of a range of X-autosome translocations in DMD females, all disrupting the short arm of the X-chromosome at Xp21, clearly pointed to this region as harboring the gene involved in DMD (e.g. Verellen [1978] acc. to Boyd [1986], Lindenbaum [1979] Boyd [1986]). In addition, these reports suggested that, due to the translocation, the locus on the normal X was inactivated.
Later, a translocation was also instrumental in the isolation of the DMD-gene itself. Worton (1984) studied a DMD female which carried a X;21 translocation (originally described by Verellen-Dumoulin (1984). This translocation turned out to split the large block of ribosomal RNA genes on the short arm of chromosome 21. Consequently, rRNA gene probes could be used to identify and clone the translocation junction fragment which contained both rRNA gene sequences and segments of the X-chromosome at or near the DMD locus (Ray [1985]). The DNA fragment derived from the X-chromosomal portion, designated XJ1.1 (DXS206), detected a TaqI-RFLP closely linked to the DMD gene and it uncovered a chromosomal deletion in a male DMD patient.
Detailed analysis of several translocation breakpoints in the DMD-gene which were characterized down to the sequence level did not reveal any clear relation with the structure or sequence of the region at or flanking the region involved (Bodrug [1987], Giacalone & Francke[1992], van Bakel [1995]). Frequently, the translocation seems to involve the deletion of sequences at the translocation junction. These deletions are mostly a few basepairs, Giacalone & Francke (1992) reported a 5 kb deletion in intron 16 associted with a X;4 translocation.
The parental origin of the de novo X-autosome translocations in DMD females studied thus far were all of paternal origin (9 / 9 analysed); Giacalone & Francke [1992] and Kean (1986) each used RFLP and Southern analysis to characterize one case, Robinson (1990) methylation analysis using the X-linked probe M27 beta to characterize 3 cases and Bodrug (1991) polymorphic markers to characterize two cases.
| Translocation | Position in DMD gene | Cell line | Phenotype | Reference | Remark |
|---|---|---|---|---|---|
| X;8 (p11.4;q24.2) | 5' of gene (754) | LOS | no DMD | Hofker (1986) | |
| X;1 (p21;p34) | intron 7 | WLS | DMD | Cockburn DJ (1991), thesis PhD thesis Univ. Oxford | cloned and sequenced by Cockburn (GenBank Z21689) |
| X;1(p21.2;q34.1-3) (invXp11.4-Xp21.2) |
DMD | Lindenbaum (1979) | |||
| X;2 (p21;q14) | Zatz acc. Boyd (1986) | ||||
| X;2 (p21.2;q37.3) | intron 63 | Holden (1986) | moderate mental retardation; cloned/sequenced by Bodrug (1991) (GenBank M62512, M62513); paternal origin | ||
| X;3 (p21;q27) | Pearson acc. Boyd (1986) | ||||
| X;3 (p21.2;q13.3) | SfiI-GH | VSN | girl with DMD, MR and dysmorphic signs | Canki (1979) acc. Boyd (1986) | mother thought to be heterozygous. |
| X;4 (p21.1;q26) | female with DMD | Saito (1985) | |||
| X;4 (p21.2;q31.22) | intron 16 | 4 year girl with DMD | Giacalone & Francke (1992) | cloned and sequenced, includes ~5 kb deletion. De novo translocation of paternal origin | |
| X;4 (p21;q35) | intron 51 | Bodrug (1989) | cloned/sequenced by Bodrug (1991) (GenBank M62514, M62515); paternal origin | ||
| X;5 (p21.2;q31.1) | intron 51 | HEM | female with DMD | Nevin (1986) | moderate MR, cloned and sequenced; cloned and sequenced by van Bakel (1995) |
| X;5 (p21.1;q35.3) | intron 1 | LUM | female with DMD and MR | Jacobs (1981) | mapped by Bodrug (1989) |
| X;6 (p21;q16) | female with DMD | Perez Vidal (1983) acc. Boyd (1986) | |||
| X;6 (p21.2;q21) | SfiI-EF | EDN | female with DMD | Zatz (1981) | |
| X;8 (p21.1;q24.3) | SfiI-EF | KIY | female with mild DMD | Narazaki (1985) | |
| X;9 (p21;p21) | girl with DMD | Bjerglund (1984) | Turner's syndrome, epilepsy, mental retardation | ||
| X;9 (p21.2;p22.3) | girl with DMD | Bjerglund (1983) acc. Boyd (1986) | moderate mental retardation | ||
| X;11 (p21.1;q13.5) | intron 1 | 16-year-old girl | Greenstein (1977) acc. Boyd 1986 | mother not a carrier, mapped by Bodrug (1989) | |
| X;11 (p21.2;q23.3) | SfiI-EF | LAR | female with mild DMD | Bjerglund (1983) acc. Boyd 1986 | |
| X;15 (p21;q26) | Ribiero acc. to Boyd 1986 | parents first cousins | |||
| X;19 (p21.2;q12) | SfiI-HJ | ORI | female with DMD | Boyd (1986) | |
| X;21 (p21.1;p12) | intron 7 | FRA | female with mild DMD | Verellen-Dumoulin (1984), Worton (1984) | translocation splits block ribosomal RNA genes, cloned by Ray (1985), sequenced by Bodrug (1987) (GenBank M18740 / M18023) |
| X;22 (p21;q13) | SfiI-EG | DEB | female with DMD | Zatz acc. to Boyd (1986) | |
| X;22 (p21.2;q13.3) | 3' of gene | KOG | no DMD | Boyd (1986) | |
Legend:
Position in DMD gene: location of translocation breakpoint in the DMD
gene;
bold italics = translocation breakpoint sequenced and listed in the DMD gene mutation database.
Cell line: as reported in Meitinger
(1988).
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