Genetic analysis of choroideremia families in the Australian population.
BACKGROUND
Choroideremia is an X-linked inherited chorioretinal disease known to be caused by mutations in the CHM gene. In this study, Australian families clinically diagnosed with choroideremia were genetically analysed for mutations in the CHM gene.


METHODS
The Australian Inherited Retinal Disease Register and DNA Bank (AIRDR) was investigated to identify a cohort of choroideremia-affected families for genetic analysis.


METHODS
Participants were sourced from the AIRDR. Thirty-two participants (15 affected, 10 carriers, 7 unaffected) sourced from 11 unrelated families having at least one member clinically diagnosed with choroideremia were included in the study.


METHODS
We performed sequence analysis of the CHM gene on the DNA of nine probands. We received the direct sequencing results of two probands by other means. Targeted analysis was subsequently performed for all 32 participants to confirm the direct sequencing results in the 11 probands and to establish the presence or absence of the implicated mutation in the remaining 21 affected, carrier or unaffected family members.


METHODS
Genetic characterisation of 11 choroideremia families in the Australian population.


RESULTS
A CHM mutation was detected in all 11 families. Each family had a different mutation. Mutations segregated within each family according to disease status. Five mutations were novel and six have been previously reported.


CONCLUSIONS
Six previously reported and five novel CHM mutations were detected in 11 Australian families clinically diagnosed with choroideremia. We anticipate that this work will facilitate access for AIRDR participants and their progeny to CHM gene therapy trials.
Australian Inherited Retinal Disease Register and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
Terri L
TL
McLaren
Australian Inherited Retinal Disease Register and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
John N
JN
De Roach
Australian Inherited Retinal Disease Register and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
Hannah
H
Montgomery
Australian Inherited Retinal Disease Register and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
Ling
L
Hoffmann
Australian Inherited Retinal Disease Register and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
Caitlyn
C
Kap
Australian Inherited Retinal Disease Register and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
Tina M
TM
Lamey
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001315:Australia / Q000453:epidemiology; D001483:Base Sequence; D002648:Child; D015794:Choroideremia / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012042:Registries; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; C081787:CHM protein, human
CHM; REP1; choroideremia; rab escort protein 1