TY - JOUR
T1 - The genetic profile of Leber congenital amaurosis in an Australian cohort
AU - Thompson, Jennifer A.
AU - De Roach, John N.
AU - McLaren, Terri L.
AU - Montgomery, Hannah E.
AU - Hoffmann, Ling H.
AU - Campbell, Isabella R.
AU - Chen, Fred K.
AU - Mackey, David A.
AU - Lamey, Tina M.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - BACKGROUND: Leber congenital amaurosis (LCA) is a severe visual impairment responsible for infantile blindness, representing ~5% of all inherited retinal dystrophies. LCA encompasses a group of heterogeneous disorders, with 24 genes currently implicated in pathogenesis. Such clinical and genetic heterogeneity poses great challenges for treatment, with personalized therapies anticipated to be the best treatment candidates. Unraveling the individual genetic etiology of disease is a prerequisite for personalized therapies, and could identify potential treatment candidates, inform patient management, and discriminate syndromic forms of disease.METHODS: We have genetically analyzed 45 affected and 82 unaffected individuals from 34 unrelated LCA pedigrees using predominantly next-generation sequencing and Array CGH technology.RESULTS: We present the molecular findings for an Australian LCA cohort, sourced from the Australian Inherited Retinal Disease Registry & DNA Bank. CEP290 and GUCY2D mutations, each represent 19% of unrelated LCA cases, followed by NMNAT1 (12%). Genetic subtypes were consistent with other reports, and were resolved in 90% of this cohort.CONCLUSION: The high resolution rate achieved, equivalent to recent findings using whole exome/genome sequencing, reflects the progression from hypothesis (LCA Panel) to non-hypothesis (RD Panel) testing and, coupled with Array CGH analysis, is a highly effective first-tier test for LCA.
AB - BACKGROUND: Leber congenital amaurosis (LCA) is a severe visual impairment responsible for infantile blindness, representing ~5% of all inherited retinal dystrophies. LCA encompasses a group of heterogeneous disorders, with 24 genes currently implicated in pathogenesis. Such clinical and genetic heterogeneity poses great challenges for treatment, with personalized therapies anticipated to be the best treatment candidates. Unraveling the individual genetic etiology of disease is a prerequisite for personalized therapies, and could identify potential treatment candidates, inform patient management, and discriminate syndromic forms of disease.METHODS: We have genetically analyzed 45 affected and 82 unaffected individuals from 34 unrelated LCA pedigrees using predominantly next-generation sequencing and Array CGH technology.RESULTS: We present the molecular findings for an Australian LCA cohort, sourced from the Australian Inherited Retinal Disease Registry & DNA Bank. CEP290 and GUCY2D mutations, each represent 19% of unrelated LCA cases, followed by NMNAT1 (12%). Genetic subtypes were consistent with other reports, and were resolved in 90% of this cohort.CONCLUSION: The high resolution rate achieved, equivalent to recent findings using whole exome/genome sequencing, reflects the progression from hypothesis (LCA Panel) to non-hypothesis (RD Panel) testing and, coupled with Array CGH analysis, is a highly effective first-tier test for LCA.
KW - Genetic variants
KW - inherited retinal dystrophies
KW - Leber congenital amaurosis
KW - next-generation sequencing
KW - personalized therapies
KW - retinal disease
UR - http://www.scopus.com/inward/record.url?scp=85040643005&partnerID=8YFLogxK
U2 - 10.1002/mgg3.321
DO - 10.1002/mgg3.321
M3 - Article
C2 - 29178642
AN - SCOPUS:85040643005
SN - 2324-9269
VL - 5
SP - 652
EP - 667
JO - Molecular genetics & genomic medicine
JF - Molecular genetics & genomic medicine
IS - 6
ER -