Whole exome sequencing identifies a heterozygous missense variant in the PRDM5 gene in a family with Axenfeld–Rieger syndrome

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• 作者：Shazia Micheal ; Sorath Noorani Siddiqui ; Saemah Nuzhat Zafar…
• 关键词：Axenfeld–Rieger syndrome ; Whole exome sequencing ; PRDM5
• 刊名：neurogenetics
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：17
• 期：1
• 页码：17-23
• 全文大小：634 KB
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• 作者单位：Shazia Micheal (1)
  Sorath Noorani Siddiqui (2)
  Saemah Nuzhat Zafar (2)
  Hanka Venselaar (3)
  Raheel Qamar (4) (5)
  Muhammad Imran Khan (6)
  Anneke I. den Hollander (1) (6)
  
  1. Department of Ophthalmology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
  2. Department of Pediatric Ophthalmology, Al-Shifa Eye Trust Hospital Jhelum Road, Rawalpindi, Pakistan
  3. Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
  4. Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan
  5. Al-Nafees Medical College and Hospital, Isra University, Islamabad, Pakistan
  6. Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Neurosciences
  Human Genetics
  Molecular Medicine
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1364-6753

文摘

Axenfeld–Rieger syndrome (ARS) is a disorder affecting the anterior segment of the eye, often leading to secondary glaucoma and several systemic malformations. It is inherited in an autosomal dominant fashion that has been associated with genetic defects in PITX2 and FOXC1. Known genes CYP1b1, PITX2, and FOXC1 were excluded by Sanger sequencing. The purpose of current study is to identify the underlying genetic causes in ARS family by whole exome sequencing (WES). WES was performed for affected proband of family, and variants were prioritized based on in silico analyses. Segregation analysis of candidate variants was performed in family members. A novel heterozygous PRDM5 missense variant (c.877A>G; p.Lys293Glu) was found to segregate with the disease in an autosomal dominant fashion. The novel missense variant was absent from population-matched controls, the Exome Variant Server, and an in-house exome variant database. The Lys293Glu variant is predicted to be pathogenic and affects a lysine residue that is conserved in different species. Variants in the PRDM5 gene were previously identified in anterior segment defects, i.e., autosomal recessive brittle cornea syndrome and keratoconus. The results of this study suggest that genetic variants in PRDM5 can lead to various syndromic and nonsyndromic disorders affecting the anterior segment of the eye. Keywords Axenfeld–Rieger syndrome Whole exome sequencing PRDM5