Mutation Screening of the CYP1B1 Gene Reveals Novel and Recurrent Pathogenic Variants in Pakistani Primary Congenital Glaucoma Patients

Authors

  • Waqas Ali Surhio
  • Feriha Fatima Khidri
  • Mohsin Iqbal Haroon
  • Samia Mehmood
  • Yar Mohammad Waryah

Keywords:

CYP1b1, Primary congenital glaucoma, consanguineous pedigree, PCG mutation, Sequencing/diagnostic testing

Abstract

OBJECTIVE: To identify the pathogenic alleles in primary congenital glaucoma patients for early cure of the disease  

METHODology:  A cross-sectional descriptive study was carried out after approval from the ethical committee of SIOVS from December 2022 to November 2023 at Sindh Institute of Ophthalmology & Visual Sciences, Hyderabad. The consanguineous pedigree consisting of more than one affected was included, and the pedigree consists only one affected or secondary cause of vision loss was excluded. After getting informed consent, ten cc blood samples from all available participants in the pedigree were drawn, and DNA was extracted. The ARMS Assay and Sanger sequencing methods were adapted to analyze the CYP1B1 gen.

Results: In the present study, one novel c.1187C>T, p.Pro396Leu and one reported c.1169G>A, p.Arg390His allele in CYP1B1 gene were found in two isolated pedigrees enrolled from Sindh Pakistan. ARMS Assay method and the Sanger sequencing method were adopted to detect pathogenic variants. Bioinformatics tools were used to analyze the pathogenesis of identified alleles and compare phenotype-genotype correlation.

CONCLUSION:  The findings of novel and frequently reported mutations have a significant role in advancing genetic testing protocols, enabling more accurate targeting of diagnoses and identified alleles that may be added to existing repositories of the genetic database.

References

Rauf B, Khan SY, Jiao X, Irum B, Ashfaq R, Zehra M et al. Next-generation whole exome sequencing to delineate the genetic basis of primary congenital glaucoma. Sci Rep. 2022; 12: 17218. doi: 10.1038/s41598-022-20939-5.

Dietze J, Blair K, Havens SJ. Glaucoma. StatPearls. Treasure Island FL ineligible companies. Disclosure: Kyle Blair declares no relevant financial relationships with ineligible companies. Disclosure: Shane Havens declares no relevant financial relationships with ineligible companies.: 2024; StatPearls Publishing LLC.

Shah M, Bouhenni R, Benmerzouga I. Geographical Variability in CYP1B1 Mutations in Primary Congenital Glaucoma. J Clin Med. 2022; 11(7): 2048. doi: 10.3390/jcm11072048.

Tehreem R, Arooj A, Siddiqui SN, Naz S, Afshan K, Firasat S. Mutation screening of the CYP1B1 gene reveals thirteen novel disease-causing variants in consanguineous Pakistani families causing primary congenital glaucoma. PloS One. 2022; 17(9): e0274335. doi: 10.1371/journal.pone.0274335.

Shah BR, Xu W, Mraz J. Cytochrome P450 1B1: role in health and disease and effect of nutrition on its expression. RSC Adv. 2019; 9(36): 21050-21062. doi: 10.1039/c9ra03674a.

Jubair S, Al-Rubai'i SH, Al-Sharifi AN, Suleiman AAJ. Investigation of CYP1B1 Gene Involvement in Primary Congenital Glaucoma in Iraqi Children. Middle East Afr J Ophthalmol. 2019; 26(4): 203-9. doi: 10.4103/meajo.MEAJO_116_19.

Choudhary D, Jansson I, Stoilov I, Sarfarazi M, Schenkman JB. Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1b1. Drug Metab Dispos. 2004; 32(8): 840-7. doi: 10.1124/dmd.32.8.840.

Kupfer C, Kaiser-Kupfer MI. New hypothesis of developmental anomalies of the anterior chamber associated with glaucoma. Trans Ophthalmol Soc U K. 1978; 98(2): 213-5.

Badawi AH, Al-Muhaylib AA, Al Owaifeer AM, Al-Essa RS, Al-Shahwan SA. Primary congenital glaucoma: An updated review. Saudi J Ophthalmol. 2019; 33(4): 382-8. doi: 10.1016/j.sjopt.2019.10.002. Epub 2019 Nov 7.

Grimberg J, Nawoschik S, Belluscio L, McKee R, Turck A, Eisenberg A. A simple and efficient non-organic procedure for the isolation of genomic DNA from blood. Nucleic Acids Res. 1989; 17(20): 8390. doi: 10.1093/nar/17.20.8390.

Abdalla M, El-Arabey AA, Gai Z. Hypertension is still a moving target in the context of COVID-19 and post-acute COVID-19 syndrome. J Med Virol. 2023; 95(1): e28128.

Ansar M, Chung H, Waryah YM, Makrythanasis P, Falconnet E, Rao AR et al. Visual impairment and progressive phthisis bulbi caused by recessive pathogenic variant in MARK3. Hum Mol Genet. 2018; 27(15): 2703-11. doi: 10.1093/hmg/ddy180.

Waryah YM, Iqbal M, Sheikh SA, Baig MA, Narsani AK, Atif M et al. Two novel variants in CYP1B1 gene: a major contributor of autosomal recessive primary congenital glaucoma with allelic heterogeneity in Pakistani patients. Int J Ophthalmol. 2019; 12(1): 8-15. doi: 10.18240/ijo.2019.01.02.

Mandal AK, Chakrabarti D, Gothwal VK. Approach to primary congenital glaucoma: A perspective. Taiwan J Ophthalmol. 2023; 13(4): 451-60. doi: 10.4103/tjo.TJO-D-23-00104.

Kaur K, Gurnani B. Primary Congenital Glaucoma. In: Statpearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan.

Rashid M, Yousaf S, Sheikh SA, Sajid Z, Shabbir AS, Kausar T et al. Identities and frequencies of variants in CYP1B1 causing primary congenital glaucoma in Pakistan. Mol Vis. 2019; 25: 144-54.

Kaushik S, Choudhary S, Kaur A, Srivastava P, Pokharel B, Akella M et al. Neonatal-Onset Congenital Ectropion Uveae May Be Caused by a Distinct CYP1B1 Pathologic Variant. Am J Ophthalmol. 2022; 239: 54-65. doi: 10.1016/j.ajo.2022.01.014. Epub 2022 Jan 24.

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Published

28-06-2024

How to Cite

1.
Waqas Ali Surhio, Feriha Fatima Khidri, Mohsin Iqbal Haroon, Samia Mehmood, Waryah YM. Mutation Screening of the CYP1B1 Gene Reveals Novel and Recurrent Pathogenic Variants in Pakistani Primary Congenital Glaucoma Patients. J Liaq Uni Med Health Sci [Internet]. 2024 Jun. 28 [cited 2024 Dec. 22];23(02):140-5. Available from: http://121.52.154.205/index.php/jlumhs/article/view/1362

Issue

Vol. 23 No. 02 (2024): Journal of Liaquat University of Medical & Health Sciences

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Original Articles

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