CYP1B1 mutations in patients with primary congenital glaucoma from Saudi Arabia

BMC Medical Genetics

Manal T Hedrawi²  Anneke I den Hollander¹  Robert K Koenekoop³  Shazia Micheal¹  Osama M Badeeb⁴ 

[1] Departments of Ophthalmology and Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands;Pediatric Ophthalmology unit, King Fahd armed forces hospital, Jeddah, Saudi Arabia;McGill Ocular Genetics Laboratory, Pediatric Ophthalmology unit, McGill University Health Center, Montreal, QC, Canada;Glaucoma unit, College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

关键词: CYP1B1;    Mutation;    Gene;    Glaucoma;    Congenital;   

Others  :  1090666
DOI  :  10.1186/s12881-014-0109-2

 received in 2014-02-03, accepted in 2014-09-24,  发布年份 2014

【 摘 要 】

Background

CYP1B1 is the most commonly mutated gene in primary congenital glaucoma (PCG). This study was undertaken to identify mutations in CYP1B1 in the Western region of Saudi Arabia.

Methods

Blood of patients who had typical findings of PCG, were screened by direct sequencing of all coding exons and splice junctions of the CYP1B1 gene.

Results

34 patients were studied; 18 patients belonged to 8 families, and 16 patients were non-familial, isolated PCG. Consanguinity was found in 27/34 (79.4%) of cases. All patients were diagnosed to have bilateral PCG at birth except one child, who had glaucoma in the right eye. More males (61.8%) were affected than females (38.2%). 79.4% (27/34) of patients were solved with pathogenic mutations and 20.6% (7/34) remained unsolved. Of the solved ones, 22.2% (6/27) of patients carry a pathogenic allele on one allele while the other allele remained yet to be determined. Direct sequencing of exon 2 revealed two pathogenic variants (p.Gly61Glu, p.Glu229Lys). P.Gly61Glu substitution was found both homozygously in 63% (17/27) of cases, and heterozygously in one patient. P.Glu229Lys variant was found heterozygous in 3.7% (1/27) of cases. One pathogenic variant (p.Arg469Trp) was found in exon 3, and is present homozygously in 14.8% (4/27) of cases while four patients have this variant heterozygously. All mutations were reported previously in the Saudi population, except p.Glu229Lys. Severe cases were associated with p.Gly61Glu, and p.Arg469Trp in 50% and 30% of ten patients respectively.

Conclusions

This study confirms that CYP1B1 mutations are the most frequent cause of PCG in the Saudi population, with p.Gly61Glu being the major disease-associated mutation. P.Glu229Lys is a newly discovered mutation in our PCG patients. Patient lacking mutation in CYP1B1 gene seems likely, to have another genetic loci involved in the pathogenesis of the disease, and need further study. Genetic studies of recessive diseases such as PCG is important in consanguineous populations, since it will increase awareness and allows genetic counseling to be offered to patients and their relatives. This will not only reduce the disease to be inherited to future generations, but will also reduce the disease burden in the community.

【 授权许可】

   
2014 Badeeb et al.; licensee BioMed Central Ltd.

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