The SOX2 anophthalmia syndrome is emerging as a clinically recognizable disorder that has been identified in 10–15% of individuals with bilateral anophthalmia. Extra-ocular anomalies are common. The majority of SOX2 mutations identified appear to arise de novo in probands ascertained through the presence of anophthalmia or microphthalmia. In this report, we describe two sisters with bilateral anophthalmia/microphthalmia, brain anomalies and a novel heterozygous SOX2 gene single-base pair nucleotide deletion, c.551delC, which predicts p.Pro184ArgfsX19. The hypothetical protein product is predicted to lead to haploinsufficient SOX2 function. Mosaicism for this mutation in the SOX2 gene was also identified in their clinically unaffected mother in peripheral blood DNA. Thus it cannot be assumed that all SOX2 mutations in individuals with anophthalmia /microphthalmia are de novo. Testing of parents is indicated when a SOX2 mutation is identified in a proband.

Tay-Sachs disease (TSD) carrier screening, initiated in the 1970s, has reduced the birth-rate of Ashkenazi Jews with TSD worldwide by 90%. Recently, several nationwide programs have been established that provide carrier screening for the updated panel of Jewish genetic diseases on college campuses and in Jewish community settings. The goals of this study were to determine the performance characteristics of clinical TSD testing in college- and community-based screening programs and to determine if molecular testing alone is adequate in those settings. Clinical data for TSD testing were retrospectively anonymized and subsequently analyzed for 1,036 individuals who participated in these programs. The performance characteristics of the serum and the platelet Hexosaminidase assays were compared, and also correlated with the results of targeted DNA analysis. The serum assay identified 29 carriers and the platelet assay identified 35 carriers for carrier rates of 1/36 and 1/29, respectively. One hundred sixty-nine samples (16.3%) were inconclusive by serum assay in marked contrast to four inconclusive samples (0.4%) by the platelet assay. Molecular analysis alone would have missed four of the 35 carriers detected by the platelet assay, yielding a false negative rate of 11.4% with a sensitivity of 88.6%. Based on the results of this study, platelet assay was superior to serum with a minimal inconclusive rate. Due to changing demographics of the Ashkenazi Jewish population, molecular testing alone in the setting of broad-based population screening programs is not sufficient, and biochemical analysis should be the assay of choice.

Axenfeld-Rieger spectrum (ARS) includes the anterior segment abnormalities posterior embryotoxon, irido-corneal adhesions, corectopia, and other abnormalities of pupil size and shape. Glaucoma occurs in approximately 50% of affected children. It is often caused by mutations of FOXC1 or PITX2. Timing of expression and dosage of these transcription factors appear to be very critical in the development of the anterior segment. We report on one child with a deletion and another with a duplication involving 6p25, causing an anirdia-like phenotype. Classic anirdia is a pan-ophthalmic disorder caused by heterozygous mutations involving the paired homeobox gene PAX6 at 11p13. It is often associated with optic nerve hypoplasia, foveal hypoplasia, corneal pannus, nystagmus, and cataract. Microdeletion of 11p13 may be associated with life threatening Wilms tumor. Distinguishing these two syndromes has critical implications for prognosis and treatment. We demonstrate how chromosomal microarray can be instrumental in differentiating these phenotypes.