Interstitial deletion 14q22.3-q23.2: genotype-phenotype correlation.

The increasing use of molecular tools in genetic diagnosis has produced a surge in the detection of genomic imbalances. Among the growing number of newly discovered chromosome alterations are the interstitial deletions 14q21-q23. In previous reports of this deletion, the patients appear to share ocular defects, pituitary alterations and hand/foot anomalies. Here, we present a 12-year-old girl with dysmorphic face, choanal atresia, gastroesophageal reflux, and moderate developmental delay, in whom an interstitial deletion 14q22.3-q23.2 was detected using a 180k array comparative genome hybridization. The 6.5 Mb deletion contains 27 genes, including three genes of the SIX family: SIX1, SIX4, and SIX6. In mammals, Six1 has been shown to be involved in ocular differentiation, whereas Six4 and Six6 are primarily expressed in the hypothalamus, pituitary gland, and facial bones. We used data on mouse embryos to evaluate the expression of the SIX genes, as well as other representative genes lost in the current patient and a previously published case with a similar phenotype, in order to correlate their pattern of expression with the functional anomalies that constitute the patient's phenotype. We also explored the possibility of other genetic influences, such as the existence of an imprinted region in chromosome 14q, which may provide a better understanding of the observed clinical variability.