Molecular Characterization of Newborn Glaucoma Including a Distinct Aniridic Phenotype

Abstract

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.

Mutations of the CYP1B1 gene in congenital anterior staphylomas

“…These phenotypes are typically associated with glaucoma 14,18. Homozygous or compound heterozygous CYP1B1 mutations were identified in eight probands with mild ectropion uvea, partial aniridia, and congenital glaucoma,19 and now this report further expands the ocular phenotype associated with CYP1B1 mutations.…”

CYP1B1 analysis of unilateral primary newborn glaucoma in Saudi children

“…1,5,6 For both CYP1B1-related and CYP1B1-negative unilateral primary congenital glaucoma, the contralateral eye remains a lifelong glaucoma suspect because variable expressivity is a recognized phenomenon. 2,4,5 In addition, unilateral newborn glaucoma should raise a high index of suspicion for secondary cause in the involved eye. This suspicion should continue through the first few years of life, as exemplified by the case that was excluded from our study after one year of follow-up because of a later diagnosis of ipsilateral orbitofacial neurofibromatosis.…”

“…In our CYP1B1-negative unilateral cases, the underlying etiology or etiologies may be identical to what underlies the 8% to 9% of bilateral primary newborn and infantile glaucoma cases that are CYP1B1-negative in Saudi Arabia. [2][3][4] One potential mechanism for unilateral newborn glaucoma is local mosaicism in the affected orbit, but this is difficult to prove without a tissue biopsy. Another possibility is the occurrence of CYP1B1 mutations not detectable by our methods, such as deep intronic, regulatory element, or large genomic rearrangement mutations.…”

“…CYP1B1 sequencing methods have been described elsewhere. 2 In brief, polymerase chain reaction was used to amplify coding exons and flanking intronic sequences for bidirectional sequencing.…”

Complete Aniridia with Central Keratopathy and Congenital Glaucoma is aCYP1B1-related Phenotype

“…1 The child and his immediate family were invited to participate in and underwent informed consent for a study protocol of autozygosity analysis guided candidate gene testing under the assumption that his phenotype was caused by an underlying recessive mutation.…”