TY - CHAP
T1 - Analysis of the ABCA4 c.[2588G>C;5603A>T] Allele in the Australian Population
AU - Thompson, Jennifer A.
AU - Chiang, John (Pei Wen)
AU - De Roach, John N.
AU - McLaren, Terri L.
AU - Chen, Fred K.
AU - Hoffmann, Ling
AU - Campbell, Isabella
AU - Lamey, Tina M.
N1 - Funding Information:
The Australian Inherited Retinal Disease Registry and DNA Bank is financially supported by Retina Australia. The support of the Registry participants, ophthalmologists and the Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, is gratefully acknowledged. FKC is supported by the National Health and Medical Research Council of Australia (grants 1142962 and 1116360).
Funding Information:
Acknowledgements The Australian Inherited Retinal Disease Registry and DNA Bank is financially supported by Retina Australia. The support of the Registry participants, ophthalmologists and the Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, is gratefully acknowledged. FKC is supported by the National Health and Medical Research Council of Australia (grants 1142962 and 1116360).
Publisher Copyright:
© 2019, Springer Nature Switzerland AG.
PY - 2019
Y1 - 2019
N2 - Inherited retinal diseases (IRDs) are genetically and phenotypically diverse, and they cause significant morbidity worldwide. Importantly, IRDs may be amenable to precision medicine strategies, and thus the molecular characterisation of causative variants is becoming increasingly important with the promise of personalised therapies on the horizon. ABCA4, involved in the translocation of visual cycle derivatives, is a well-established, frequent cause of IRDs worldwide, with pathogenic variants implicated in phenotypically diverse diseases. Identification of causative ABCA4 variants in some individuals, however, has been enigmatic, and resolution of this issue is currently a hotbed of research. Recent evidence has indicated that hypomorphic alleles, which cause disease under certain conditions, may account for some of the missing causal variants. It has been postulated that the ABCA4 c.5603A>T (p.Asn1868Ile) variant, previously considered benign, be reclassified as hypomorphic when in cis configuration with c.2588G>C (p.Gly863Ala/Gly863del), a variant previously considered to be pathogenic in its own right. We are exploring this relationship within an Australian cohort to test this theory.
AB - Inherited retinal diseases (IRDs) are genetically and phenotypically diverse, and they cause significant morbidity worldwide. Importantly, IRDs may be amenable to precision medicine strategies, and thus the molecular characterisation of causative variants is becoming increasingly important with the promise of personalised therapies on the horizon. ABCA4, involved in the translocation of visual cycle derivatives, is a well-established, frequent cause of IRDs worldwide, with pathogenic variants implicated in phenotypically diverse diseases. Identification of causative ABCA4 variants in some individuals, however, has been enigmatic, and resolution of this issue is currently a hotbed of research. Recent evidence has indicated that hypomorphic alleles, which cause disease under certain conditions, may account for some of the missing causal variants. It has been postulated that the ABCA4 c.5603A>T (p.Asn1868Ile) variant, previously considered benign, be reclassified as hypomorphic when in cis configuration with c.2588G>C (p.Gly863Ala/Gly863del), a variant previously considered to be pathogenic in its own right. We are exploring this relationship within an Australian cohort to test this theory.
KW - ABCA4
KW - Australian Inherited Retinal Disease Registry
KW - Hypomorphic
KW - Inherited retinal disease
KW - Molecular genetics
KW - Next generation sequencing
KW - Sanger sequencing
KW - c.5603A>T
UR - http://www.scopus.com/inward/record.url?scp=85077302529&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077302529&partnerID=8YFLogxK
U2 - 10.1007/978-3-030-27378-1_44
DO - 10.1007/978-3-030-27378-1_44
M3 - Chapter
C2 - 31884623
AN - SCOPUS:85077302529
T3 - Advances in Experimental Medicine and Biology
SP - 269
EP - 273
BT - Advances in Experimental Medicine and Biology
PB - Springer
ER -