A case of deletion 14(q22.1--&gt;q22.3) associated with anophthalmia and pituitary abnormalities.

Elliott, J. Richard; Maltby, E L; Reynolds, Benedict M.

doi:10.1136/jmg.30.3.251

Cited by 64 publications

(56 citation statements)

References 7 publications

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“…Analysis of patients with interstitial deletions of 14q22-23 and a t(3;14)(q28;q23.2) patient led to the identification of OTX2 as a candidate disease gene in anophthalmia (Bennett et al, 1991;Elliott et al, 1993;Lemyre et al, 1998;Nolen et al, 2006). OTX2 is a bicoid-type homeodomain transcription factor important in retinal differentiation and fore and midbrain development (Bovolenta et al, 1997;Simeone et al, 1993).…”

Section: Otx2mentioning

confidence: 99%

Chromosomal Rearrangements and Novel Genes in Disorders of Eye Development, Cataract and Glaucoma

et al. 2008

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Disorders of eye development such as microphthalmia and anophthalmia (small and absent eyes respectively), anterior segment dysgenesis where there may be pupillary and iris anomalies, and associated cataract and glaucoma, often lead to visual impairment or blindness. Currently treatment options are limited, as much is unknown about the molecular pathways that control normal eye development and induce the aberrant processes that lead to ocular defects. Mutation detection rates in most of the known genes are generally low, emphasizing the genetic heterogeneity of developmental ocular defects. Identification of the disease genes in these conditions improves the clinical information available for affected individuals and families, and provides new insights into the underlying biological processes for facilitation of better treatment options. Investigation of chromosomal rearrangements associated with an ocular phenotype has been especially powerful for disease gene identification. Molecular characterization of such rearrangements, which pinpoints the region by physically disrupting the causative gene or its regulatory sequences, allows for rapid elucidation of underlying genetic factors that contribute to the phenotype. Genes including PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4 have been identified in this way to be associated with developmental eye disorders. More recently, new methods in chromosomal analysis such as comparative genomic hybridization (CGH) microarray, have also enhanced our ability in disease gene identification.

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Section: Otx2mentioning

confidence: 99%

Chromosomal Rearrangements and Novel Genes in Disorders of Eye Development, Cataract and Glaucoma

et al. 2008

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“…The first described genetic defects that affected the OTX2 gene were interstitial deletions at 14q22, in association with AO and pituitary abnormalities (4,5). Using the candidate gene approach, (6,9).…”

Section: Discussionmentioning

confidence: 99%

“…A relatively large number of alterations were found to be de novo, especially in all cases with whole gene deletions and translocations (4,5,6,7,8,13,16,23). The remarkable exception to this is the duplication of 14q22.…”

Section: Discussionmentioning

confidence: 99%

“…Various genetic alterations in OTX2 have been described, including interstitial deletions (4,5), microdeletions (6,7), frameshift, and point mutations (8). The majority of the alterations are found in patients with severe ocular malformations such as anophthalmia (AO), microphthalmia (MO), Leber congenital amaurosis, or coloboma (6,8,9,10).…”

Section: Introductionmentioning

confidence: 99%

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A novel OTX2 mutation in a patient with combined pituitary hormone deficiency, pituitary malformation, and an underdeveloped left optic nerve

Blanco

Romero

Diaczok

et al. 2012

European Journal of Endocrinology

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Orthodenticle homolog 2 (OTX2) is a homeobox family transcription factor required for brain and eye formation. Various genetic alterations in OTX2 have been described, mostly in patients with severe ocular malformations. In order to expand the knowledge of the spectrum of OTX2 mutation, we performed OTX2 mutation screening in 92 patients with combined pituitary hormone deficiency (CPHD). We directly sequenced the coding regions and exon-intron boundaries of OTX2 in 92 CPHD patients from the Dutch HYPOPIT study in whom mutations in the classical CPHD genes PROP1, POU1F1, HESX1, LHX3, and LHX4 had been ruled out. Among 92 CPHD patients, we identified a novel heterozygous missense mutation c.401COG (p.Pro134Arg) in a patient with CPHD, pituitary malformation, and an underdeveloped left optic nerve. Binding of both the wild-type and mutant OTX2 proteins to bicoid binding sites was equivalent; however, the mutant OTX2 exhibited decreased transactivation. We describe a novel missense heterozygous OTX2 mutation that acts as a dominant negative inhibitor of target gene expression in a patient with CPHD, pituitary malformation, and optic nerve hypoplasia. We provide an overview of all OTX2 mutations described till date, which show that OTX2 is a promising candidate gene for genetic screening of patients with CPHD or isolated GH deficiency (IGHD). As the majority of the OTX2 mutations found in patients with CPHD, IGHD, or short stature have been found in exon 5, we recommend starting mutational screening in those patients in exon 5 of the gene.

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“…12 However, no careful description of MH structures has been provided so far in these patients. We reviewed the available brain MR midline sagittal images including the posterior cranial fossa of previously reported patients with Otx2 mutations [35][36][37][38] or chromosome 14 deletions including Otx2, [39][40][41][42][43] and we recognized a similar midbrain hypoplasia with a long pons and large superior vermis in 5 patients. 35,36,40,41,43 We therefore suggest that MH abnormalities may have been underestimated in patients with Otx2 mutations or deletion; further studies on larger series are awaited to address this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Midbrain-Hindbrain Involvement in Septo-Optic Dysplasia

Severino¹,

Allegri²,

Pistorio

et al. 2014

American Journal of Neuroradiology

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A case of deletion 14(q22.1-->q22.3) associated with anophthalmia and pituitary abnormalities.

Abstract: An interstitial deletion of the region q22

Cited by 64 publications

References 7 publications

Chromosomal Rearrangements and Novel Genes in Disorders of Eye Development, Cataract and Glaucoma

Chromosomal Rearrangements and Novel Genes in Disorders of Eye Development, Cataract and Glaucoma

A novel OTX2 mutation in a patient with combined pituitary hormone deficiency, pituitary malformation, and an underdeveloped left optic nerve

Midbrain-Hindbrain Involvement in Septo-Optic Dysplasia

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