Identification of novel CYP1B1 gene mutations in patients with primary congenital and primary open‐angle glaucoma. (23rd September 2014)

• Record Type: Journal Article
• Authors: Micheal, Shazia; Ayub, Humaira; Zafar, Saemah N; Bakker, Bjorn; Ali, Mahmood; Akhtar, Farah; Islam, Farrah; Khan, Muhammad I; Qamar, Raheel; den Hollander, Anneke I
• Is Part Of: Clinical & experimental ophthalmology. Volume 43:Number 1(2015)
• Page Start: 31
• Page End: 39
• Publication Date: 2014-09-23
• Subjects: Ophthalmology -- Periodicals; 617.7
• DOI: 10.1111/ceo.12369
• Languages: English
• ISSNs: 1442-6404

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="ceo12369-sec-0001" sec-type="section"> <title>Background</title> <p> <italic>CYP1B</italic> <italic>1</italic> is the most commonly mutated gene in primary congenital glaucoma (PCG), and mutations have also been identified in primary open‐angle glaucoma (POAG). This study was undertaken to describe mutations in <italic>CYP1B</italic><italic>1</italic> in patients and families with PCG and POAG from Pakistan.</p> </sec> <sec id="ceo12369-sec-0002" sec-type="section"> <title>Design</title> <p>Case‐control series.</p> </sec> <sec id="ceo12369-sec-0003" sec-type="section"> <title>Participants</title> <p>Forty families, 190 sporadic POAG cases and 140 controls from Pakistan.</p> </sec> <sec id="ceo12369-sec-0004" sec-type="section"> <title>Methods</title> <p>Patients and healthy individuals of one consanguineous Pakistani family were genotyped with high‐resolution single nucleotide polymorphism microarrays. Homozygosity mapping was performed using HomozygosityMapper. Direct sequencing of <italic>CYP1B</italic><italic>1</italic> gene was performed in probands of the families, sporadic POAG cases and control individuals.</p> </sec> <sec id="ceo12369-sec-0005" sec-type="section"> <title>Main Outcome Measures</title> <p>Mutations in the <italic>CYP1B</italic><italic>1</italic> gene in PCG and POAG patients.</p> </sec> <sec id="ceo12369-sec-0006" sec-type="section"> <title>Results</title> <p>Homozygosity mapping in a consanguineous Pakistani family revealed one 11‐Mb homozygous region encompassing the <italic>CYP1B</italic><italic>1</italic> gene. A homozygous <italic>CYP1B</italic><italic>1</italic> missense mutation (p.Arg390His) was identified in this family. Sequence analysis of <italic>CYP1B</italic><italic>1</italic> in 39 additional families revealed one known and three novel homozygous mutations in PCG (p.Ala288Pro, p.Asp242Ala, p.Arg355* and p.Arg290Profs*37). In POAG, one novel heterozygous missense mutation (p.Asp316Val) was identified in one family and a previously reported mutation (p.Glu229Lys) was identified in three families. Analysis of <italic>CYP1B</italic><italic>1</italic> in a panel of 190 sporadic POAG patients revealed three novel heterozygous variants (p.Thr234Lys, p.Ala287Pro and p.Gln362*) and three previously reported heterozygous variants (p.Gly61Glu, p.Glu229Lys and p.Arg368His). The p.Glu229Lys variant was significantly associated with POAG (<italic>P</italic> = 0.03; odds ratio 2.49).</p> </sec> <sec id="ceo12369-sec-0007" sec-type="section"> <title>Conclusions</title> <p>This study confirms that <italic>CYP1B</italic><italic>1</italic> mutations are associated with POAG and PCG in the Pakistani population.</p> </sec> </abstract>