Occurrence of<i>CYP1B1</i>Mutations in Juvenile Open-Angle Glaucoma With Advanced Visual Field Loss

Souzeau, Emmanuelle; Hayes, Melanie; Zhou, Tiger; Siggs, Owen M.; Ridge, Bronwyn; Awadalla, Mona S; Smith, James E.; Ruddle, Jonathan B; Elder, James E; Mackey, David A.; Hewitt, Alex W.; Healey, Paul R.; Goldberg, Ivan; Morgan, William H.; Landers, John; Dubowsky, Andrew; Burdon, Kathryn P.; Craig, Jamie E

doi:10.1001/jamaophthalmol.2015.0980

Cited by 23 publications

(22 citation statements)

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“…27,32 Four cases carried two qualifying variants in these genes. One participant was compound heterozygous and two were homozygous for CYP1B1 qualifying variants.…”

Section: Resultsmentioning

confidence: 99%

“…56 This difference may be in part due to the younger age at diagnosis in the French JOAG study (median ¼ 40, range, 13-52), as our previous study examining the prevalence of CYP1B1 variants in JOAG found a 6.8% rate. 27 Additionally, the three cases in the French study harbored a known polymorphic variant, p.(Ala443Val), which brings their true prevalence to 3.4%. The case cohort in the New Zealand study included pseudoexfoliative glaucoma and ocular hypertension as well as POAG suspects, which makes any direct comparison The data from 218 cases and 1096 controls are presented.…”

Section: Contribution Of Known Poag Genes Inmentioning

confidence: 91%

“…Moreover, JOAG participants in ANZRAG with MYOC disease-causing variants have been previously sequenced at the CYP1B1 locus, and none carried disease-causing variants in the latter gene. 27 Other limitations of this study relate to WES. The ANZRAG cases and controls were captured with a different enrichment protocol from that for the AOGC controls.…”

Section: 57mentioning

confidence: 94%

“…[19][20][21][22][23][24] CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1) disease-causing variants have been linked to both PCG and JOAG. [25][26][27] Biallelic CYP1B1 variants transmitted in an autosomal recessive manner are involved in PCG, whereas both biallelic and heterozygous variants have been involved in POAG with a lower frequency rate. Deleterious CYP1B1 variant frequency is highly variable between ethnicities: Prevalence rates of CYP1B1 variants have been reported as 4.6% in a French POAG case cohort, 26 4.62% in a Taiwanese Chinese JOAG case cohort, 28 6.8% in an Australian JOAG case cohort, 27 and 11.1% in an Iranian POAG case cohort.…”

mentioning

confidence: 99%

“…[25][26][27] Biallelic CYP1B1 variants transmitted in an autosomal recessive manner are involved in PCG, whereas both biallelic and heterozygous variants have been involved in POAG with a lower frequency rate. Deleterious CYP1B1 variant frequency is highly variable between ethnicities: Prevalence rates of CYP1B1 variants have been reported as 4.6% in a French POAG case cohort, 26 4.62% in a Taiwanese Chinese JOAG case cohort, 28 6.8% in an Australian JOAG case cohort, 27 and 11.1% in an Iranian POAG case cohort. 29 Like CYP1B1, variants in LTBP2 (latent transforming growth factor beta binding protein 2) transmitted in an autosomal recessive manner were originally linked to PCG, 30,31 with heterozygous variants later suggested in POAG.…”

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confidence: 99%

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Contribution of Mutations in Known Mendelian Glaucoma Genes to Advanced Early-Onset Primary Open-Angle Glaucoma

Zhou

Souzeau

Siggs

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Zhou T, Souzeau E, Siggs OM, et al. Contribution of mutations in known Mendelian glaucoma genes to advanced early-onset primary openangle glaucoma. Invest Ophthalmol Vis Sci. 2017;58:153758: -154458: . DOI: 10.1167 PURPOSE. Primary open-angle glaucoma (POAG) and primary congenital glaucoma (PCG) with Mendelian inheritance are caused by mutations in at least nine genes. Utilizing whole-exome sequencing, we examined the disease burden accounted for by these known Mendelian glaucoma genes in a cohort of individuals with advanced early-onset POAG. METHODS.The cases exhibited advanced POAG with young age of diagnosis. Cases and examined local controls were subjected to whole-exome sequencing. Nine hundred ninetythree previously sequenced exomes of Australian controls were called jointly with our dataset. Qualifying variants were selected based on predicted pathogenicity and rarity in public domain gene variant databases. Case-control mutational burdens were calculated for glaucoma-linked genes.RESULTS. Two hundred eighteen unrelated POAG participants and 103 nonglaucomatous controls were included in addition to 993 unexamined controls. Fifty-eight participants (26.6%) harbored rare potentially pathogenic variants in known glaucoma genes. Enrichment of qualifying variants toward glaucoma was present in all genes except WDR36, in which controls harbored more variants, and TBK1, in which no qualifying variants were detected in cases or controls. After multiple testing correction, only MYOC showed statistically significant enrichment of qualifying variants (odds ratio [OR] ¼ 16.62, P ¼ 6.31310 À16 ).CONCLUSIONS. Rare, potentially disease-causing variants in Mendelian POAG genes that showed enrichment in our dataset were found in 22.9% of advanced early-onset POAG cases. MYOC variants represented the largest monogenic cause in POAG. The association between WDR36 and POAG was not supported, and the majority of POAG cases did not harbor a potentially disease-causing variant in the remaining Mendelian genes.

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“…27,32 Four cases carried two qualifying variants in these genes. One participant was compound heterozygous and two were homozygous for CYP1B1 qualifying variants.…”

Section: Resultsmentioning

confidence: 99%

Section: Contribution Of Known Poag Genes Inmentioning

confidence: 91%

Section: 57mentioning

confidence: 94%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Contribution of Mutations in Known Mendelian Glaucoma Genes to Advanced Early-Onset Primary Open-Angle Glaucoma

Zhou

Souzeau

Siggs

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Primary congenital glaucoma due to paternal uniparental isodisomy of chromosome 2 and CYP1B1 deletion

Souzeau

Dubowsky

Ruddle

et al. 2019

Molec Gen & Gen Med

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Background CYP1B1 variants and deletions are the most common cause of primary congenital glaucoma (PCG). Methods We investigated an individual with PCG from the Australian and New Zealand Registry of Advanced Glaucoma. We performed sequencing of the CYP1B1 gene, followed by Multiplex Ligation‐dependent Probe Amplification and SNP array. Results We identified a homozygous deletion of the CYP1B1 gene by Multiplex Ligation‐dependent Probe Amplification and confirmed that the father was heterozygous for a CYP1B1 deletion but the mother had normal gene copy number. SNP array identified paternal uniparental isodisomy of the entire chromosome 2. Conclusions This study is the first report of a homozygous CYP1B1 whole gene deletion due to paternal uniparental isodisomy of chromosome 2 as a cause of PCG. These results illustrate the importance of genetic testing in providing appropriate genetic counseling regarding the risks of recurrence.

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Role of CYP1B1, p.E229K and p.R368H mutations among 120 families with sporadic juvenile onset open-angle glaucoma

Gupta

Walia

Kaur

et al. 2017

Graefes Arch Clin Exp Ophthalmol

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Occurrence ofCYP1B1Mutations in Juvenile Open-Angle Glaucoma With Advanced Visual Field Loss

Cited by 23 publications

References 44 publications

Contribution of Mutations in Known Mendelian Glaucoma Genes to Advanced Early-Onset Primary Open-Angle Glaucoma

Contribution of Mutations in Known Mendelian Glaucoma Genes to Advanced Early-Onset Primary Open-Angle Glaucoma

Primary congenital glaucoma due to paternal uniparental isodisomy of chromosome 2 and CYP1B1 deletion

Role of CYP1B1, p.E229K and p.R368H mutations among 120 families with sporadic juvenile onset open-angle glaucoma

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