A spectrum of CYP1B1 mutations associated with primary congenital glaucoma in families of Pakistani descent

Bushra Rauf, Bushra Irum, Firoz Kabir, Sabika Firasat, Muhammad Asif Naeem, Shaheen N. Khan, Tayyab Husnain, Sheikh Riazuddin, Javed Akram, Sheikh Amer Riazuddin

Research output: Contribution to journalArticle

Abstract

Glaucoma is the second leading cause of blindness, affecting ∼65 million people worldwide. We identified and ascertained a large cohort of inbred families with multiple individuals manifesting cardinal symptoms of primary congenital glaucoma (PCG) to investigate the etiology of the disease at a molecular level. Ophthalmic examinations, including slit-lamp microscopy and applanation tonometry, were performed to characterize the causal phenotype and confirm that affected individuals fulfilled the diagnostic criteria for PCG. Subsequently, exclusion analysis was completed with fluorescently labeled short tandem repeat markers, followed by Sanger sequencing to identify pathogenic variants. Exclusion analysis suggested linkage to the CYP1B1 locus, with positive two-point logarithm of odds scores in 23 families, while Sanger sequencing identified a total of 11 variants, including two novel mutations, in 23 families. All mutations segregated with the disease phenotype in their respective families. These included the following seven missense mutations: p.Y81N, p.E229K, p.R368H, p.R390H, p.W434R, p.R444Q and p.R469W, as well as one nonsense mutation, p.Q37∗, and three frameshift mutations, p.W246Lfs81∗, p.T404Sfs30∗ and p.P442Qfs15∗. In conclusion, we identified a total of 11 mutations, reconfirming the genetic heterogeneity of CYP1B1 in the pathogenesis of PCG. To the best of our knowledge, this is the largest study investigating the contribution of CYP1B1 to the pathogenesis of PCG in the Pakistani population.

Original languageEnglish (US)
Article number16021
JournalHuman Genome Variation
Volume3
DOIs
StatePublished - Aug 4 2016

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Glaucoma
Mutation
Electric lamps
Microsatellite Repeats
Microscopic examination
Phenotype
Frameshift Mutation
Genetic Heterogeneity
Nonsense Codon
Manometry
Missense Mutation
Blindness
Population

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Molecular Biology

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A spectrum of CYP1B1 mutations associated with primary congenital glaucoma in families of Pakistani descent. / Rauf, Bushra; Irum, Bushra; Kabir, Firoz; Firasat, Sabika; Naeem, Muhammad Asif; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh; Akram, Javed; Riazuddin, Sheikh Amer.

In: Human Genome Variation, Vol. 3, 16021, 04.08.2016.

Research output: Contribution to journalArticle

Rauf, B, Irum, B, Kabir, F, Firasat, S, Naeem, MA, Khan, SN, Husnain, T, Riazuddin, S, Akram, J & Riazuddin, SA 2016, 'A spectrum of CYP1B1 mutations associated with primary congenital glaucoma in families of Pakistani descent', Human Genome Variation, vol. 3, 16021. https://doi.org/10.1038/hgv.2016.21
Rauf, Bushra ; Irum, Bushra ; Kabir, Firoz ; Firasat, Sabika ; Naeem, Muhammad Asif ; Khan, Shaheen N. ; Husnain, Tayyab ; Riazuddin, Sheikh ; Akram, Javed ; Riazuddin, Sheikh Amer. / A spectrum of CYP1B1 mutations associated with primary congenital glaucoma in families of Pakistani descent. In: Human Genome Variation. 2016 ; Vol. 3.
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