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M. Mihelec, L. Nolen, D. Amor, A. Haywood, C. Willcock, L. St Heaps, J. Grigg, P. P. L. Tam, G. Peters, R. V. Jamieson; The 14q22-23 Contiguous Gene Syndrome: Phenotypic Recognition and Investigation of Candidate Anophthalmia Genes. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1313.
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Patients with interstitial deletions of 14q22-23 have bilateral anophthlamia. There are additional phenotypic features which may be unrecognised leading to delay in diagnosis and management of the associated pituitary deficiency. Our previous FISH and comparative genomic hybridisation (CGH) microarray studies in this deletion syndrome revealed deletion of genes including BMP4, OTX2, RTN1, SIX6, SIX1, and SIX4. OTX2 is involved in human ocular defects, and the very severe ocular phenotype in these patients indicates that other genes in this region may also be candidate ocular human disease genes. Our purpose in this project is to characterise the distinctive ocular, facial and pituitary features of the 14q22-23 deletion syndrome in more detail, and investigate BMP4 as a candidate gene in ocular developmental anomalies.
Clinical investigation of phenotypic features in a patient with 14q22-23 contiguous gene syndrome. Sequencing of the coding exons and surrounding intronic sequences of BMP4, in our cohort of patients with microphthalmia, anophthalmia and related ocular developmental anomalies.
A distinctive facial phenotype with high forehead, downturned corners of the mouth and small jaw can be discerned in patients with this deletion syndrome. Sequence analysis of the first 37 patients in our cohort has not so far revealed potential pathogenic mutations.
Recognition of the additional phenotypic features in these anophthlamia patients is important to prompt cytogenetic analysis, diagnosis of the 14q22-23 deletion syndrome, and pituitary investigation which has been delayed in a number of cases. BMP4 haploinsufficiency may contribute to the ocular abnormality in the 14q22-23 deletion patients since it is expressed in the early optic vesicle and is necessary for lens induction. It is also a candidate disease gene in ocular developmental disorders. Microphthalmia and anophthalmia are genetically heterogeneous conditions so we will be continuing sequence analysis in further patients.
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