Close linkage of a gene for X linked deafness to three microsatellite repeats at Xq21 in radiologically normal and abnormal families.
We have used three highly polymorphic microsatellite repeats from Xq21 to type families in whom a gene for X linked deafness with perilymphatic gusher (DFN 3) was segregating. All three markers were tightly linked to the disease in its radiologically normal and abnormal forms, with a maximum lod score of 10.37 with DXS995 and 8.44 with DXS986 at zero recombination, and 14.03 with DXS1002 at theta = 0.01. In an isolated case of deafness of this type, DXS995 indicated either the first recombination observed between the marker and the disease gene or a new mutation in the proband. Southern blotting using a cosmid fragment from the candidate region has confirmed a de novo mutation by showing a deletion in the proband which is not present in his mother as judged by dosage analysis. We also describe a family with a paracentric inversion associated with a microdeletion and discuss how deletion mapping using these and other markers in the region has helped to define a candidate region for the gene.
Bitner-Glindzicz
M
M
Unit of Clinical and Molecular Genetics, Institute of Child Health, London, UK.
de Kok
Y
Y
Summers
D
D
Huber
I
I
Cremers
F P
FP
Ropers
H H
HH
Reardon
W
W
Pembrey
M E
ME
Malcolm
S
S
D001483:Base Sequence; D017931:DNA Primers; D004276:DNA, Satellite; D003638:Deafness / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid; D014960:X Chromosome
D017931:DNA Primers; D004276:DNA, Satellite