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Molecular characterization of newborn glaucoma including a distinct aniridic phenotype.
Ophthalmic Genet. 2011 Sep; 32(3):138-42.OG

Abstract

PURPOSE

To characterize the underlying genetic defect in otherwise healthy Saudi newborns with buphthalmos, including those with iris abnormalities.

METHODS

Prospective case series of affected Saudi Arabian probands who were referred for genetic counseling over a 4 year period. All had CYP1B1 sequencing. Selected patients with visible iris abnormalities had PAX6, FOXC1, and PITX2 sequencing. CYP1B1-negative patients had LTBP2 sequencing.

RESULTS

All 67 probands had corneal enlargement with variable haze/scarring evident to caregivers at birth; 46 had a family history of infantile or early childhood glaucoma. All families were consanguineous except for 6, 2 of which were endogamous. Eight probands had mild ectropion uveae with partial aniridia; 2 probands had thick scarred corneas that precluded careful iris examination. Homozygous or compound heterozygous CYP1B1 mutations were identified in 91% (61/67), including all 8 probands with ectopion uveae and partial aniridia. The common Saudi mutation p.G61E occurred in most cases (38 homozygous, 8 compound heterozygous). Four novel mutations were identified (p.N252K, p.V460E, p.S485F, p.N519D). No mutations were identified in the other screened genes.

CONCLUSIONS

Newborn glaucoma on the Arabian Peninsula is typically CYP1B1-related even in the setting of developmental iris abnormality. Mild iris ectropion with partial aniridia in a newborn with glaucoma suggests mutations in CYP1B1 rather than in other genes associated with anterior segment dysgenesis. On the Arabian Peninsula p.G61E mutations are the major cause of newborn glaucoma but novel CYP1B1 mutations continue to be documented. The fact that the 9% of cases that were CYP1B1-negative did not have mutations in LTBP2 suggests that there exists at least 1 additional locus for this condition.

Authors+Show Affiliations

Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. arif.khan@mssm.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21306220

Citation

Khan, Arif O., et al. "Molecular Characterization of Newborn Glaucoma Including a Distinct Aniridic Phenotype." Ophthalmic Genetics, vol. 32, no. 3, 2011, pp. 138-42.
Khan AO, Aldahmesh MA, Al-Abdi L, et al. Molecular characterization of newborn glaucoma including a distinct aniridic phenotype. Ophthalmic Genet. 2011;32(3):138-42.
Khan, A. O., Aldahmesh, M. A., Al-Abdi, L., Mohamed, J. Y., Hashem, M., Al-Ghamdi, I., & Alkuraya, F. S. (2011). Molecular characterization of newborn glaucoma including a distinct aniridic phenotype. Ophthalmic Genetics, 32(3), 138-42. https://doi.org/10.3109/13816810.2010.544365
Khan AO, et al. Molecular Characterization of Newborn Glaucoma Including a Distinct Aniridic Phenotype. Ophthalmic Genet. 2011;32(3):138-42. PubMed PMID: 21306220.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular characterization of newborn glaucoma including a distinct aniridic phenotype. AU - Khan,Arif O, AU - Aldahmesh,Mohammed A, AU - Al-Abdi,Lama, AU - Mohamed,Jawahir Y, AU - Hashem,Mais, AU - Al-Ghamdi,Ismael, AU - Alkuraya,Fowzan S, Y1 - 2011/02/09/ PY - 2011/2/11/entrez PY - 2011/2/11/pubmed PY - 2011/11/10/medline SP - 138 EP - 42 JF - Ophthalmic genetics JO - Ophthalmic Genet VL - 32 IS - 3 N2 - PURPOSE: To characterize the underlying genetic defect in otherwise healthy Saudi newborns with buphthalmos, including those with iris abnormalities. METHODS: Prospective case series of affected Saudi Arabian probands who were referred for genetic counseling over a 4 year period. All had CYP1B1 sequencing. Selected patients with visible iris abnormalities had PAX6, FOXC1, and PITX2 sequencing. CYP1B1-negative patients had LTBP2 sequencing. RESULTS: All 67 probands had corneal enlargement with variable haze/scarring evident to caregivers at birth; 46 had a family history of infantile or early childhood glaucoma. All families were consanguineous except for 6, 2 of which were endogamous. Eight probands had mild ectropion uveae with partial aniridia; 2 probands had thick scarred corneas that precluded careful iris examination. Homozygous or compound heterozygous CYP1B1 mutations were identified in 91% (61/67), including all 8 probands with ectopion uveae and partial aniridia. The common Saudi mutation p.G61E occurred in most cases (38 homozygous, 8 compound heterozygous). Four novel mutations were identified (p.N252K, p.V460E, p.S485F, p.N519D). No mutations were identified in the other screened genes. CONCLUSIONS: Newborn glaucoma on the Arabian Peninsula is typically CYP1B1-related even in the setting of developmental iris abnormality. Mild iris ectropion with partial aniridia in a newborn with glaucoma suggests mutations in CYP1B1 rather than in other genes associated with anterior segment dysgenesis. On the Arabian Peninsula p.G61E mutations are the major cause of newborn glaucoma but novel CYP1B1 mutations continue to be documented. The fact that the 9% of cases that were CYP1B1-negative did not have mutations in LTBP2 suggests that there exists at least 1 additional locus for this condition. SN - 1744-5094 UR - https://www.unboundmedicine.com/medline/citation/21306220/Molecular_characterization_of_newborn_glaucoma_including_a_distinct_aniridic_phenotype_ L2 - https://www.tandfonline.com/doi/full/10.3109/13816810.2010.544365 DB - PRIME DP - Unbound Medicine ER -