Biology Reference
In-Depth Information
FIGURE 5.9. Deletion map of the X chromosome for band q21 (adapted from
Cremers et al. 1989; Bach et al. 1992; Huber et al. 1994; de Kok et al. 1996). The
position of the
POU3F4
gene, which is responsible for X-linked mixed deafness, is
marked. Solid lines represent intact chromosomal fragments. Dashed lines repre-
sent deleted regions. Patient identifiers are listed on the left. Patient phenotypes are
listed on the right. MR
= mental retardation, CH = choroideremia, DFN3 = X-linked
mixed deafness. Notice that deletions downstream of
POU3F4
also appear to cause
DFN3
consistent with a positional effect on
POU3F4
.
renal anomalies including dysplasia or aplasia of one or both kidneys, and
mild to profound hearing impairment that can be sensorineural, conductive
or mixed (OMIM 1999). The gene for BOR syndrome was cloned in 1997
(Abdelhak et al. 1997), and is the human homolog of the
Drosophila
eyes
absent gene.
EYA1
maps to 8q13, and its identification was greatly aided
by the discovery in 1989 of a family with a chromosomal rearrangement of
8q. Members of this family suffered from both BOR syndrome and Tricho-
Rhino-Phalangeal syndrome type 1 (TRPS1). Their 8q rearrangement
involved a direct insertion of DNA from 8q13-q21 into 8q24 (dir
ins(8)(q24.1q13.3q21.1)), shown in Figure 5.10 (Haan et al. 1989). TRPS1
had previously been associated with chromosomal breaks in 8q24 (Buhler
and Malik 1984; Bowen et al. 1985), suggesting that the BOR phenotype
resulted from gene disruption at either 8q13 or 8q21. Linkage analysis with
other BOR families indicated that 8q13 was the more probable locus (Wang
et al. 1994). Careful examination of 8q13 in the BOR/TRPS1 family
revealed a small deletion of less than 1 Mb at the break-point (Gu et al.
1996). Sequencing a contig spanning that break-point revealed the presence
of a novel human gene homologous to the
Drosophila
eyes-absent gene.
When the human
EYA1
gene was sequenced in other BOR patients,
