Mutations in SOX2 cause anophthalmia

Fantes, Judy; Ragge, Nicola; Lynch, Sally Ann; McGill, Niolette I.; Collin, J. R. O.; Howard‐Peebles, Patricia N.; Hayward, Caroline; Vivian, Anthony J.; Williamson, Kathy; Heyningen, Veronica van; FitzPatrick, David R.

doi:10.1038/ng1120

Cited by 482 publications

(442 citation statements)

References 14 publications

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“…41 In patients with microphthalmia/coloboma, detection rates for clear-cut pathogenic variants are generally very low, in the vicinity of 1-2% or less as found in our study. 13,42,43 A targeted NGS strategy of the known disease genes could possibly lead to a higher detection rate, as a higher depth of coverage can be achieved with this. However, where such a strategy was undertaken in the severe anophthalmia/microphthalmia group, where there is a known higher detection rate, no disease gene was identified in almost one-third of the patients.…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing in developmental eye disease leads to identification of causal variants in GJA8, CRYGC, PAX6 and CYP1B1

et al. 2013

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Developmental eye diseases, including cataract/microcornea, Peters anomaly and coloboma/microphthalmia/anophthalmia, are caused by mutations encoding many different signalling and structural proteins in the developing eye. All modes of Mendelian inheritance occur and many are sporadic cases, so provision of accurate recurrence risk information for families and affected individuals is highly challenging. Extreme genetic heterogeneity renders testing for all known disease genes clinically unavailable with traditional methods. We used whole-exome sequencing in 11 unrelated developmental eye disease patients, as it provides a strategy for assessment of multiple disease genes simultaneously. We identified five causative variants in four patients in four different disease genes, GJA8, CRYGC, PAX6 and CYP1B1. This detection rate (36%) is high for a group of patients where clinical testing is frequently not undertaken due to lack of availability and cost. The results affected clinical management in all cases. These variants were detected in the cataract/microcornea and Peters anomaly patients. In two patients with coloboma/microphthalmia, variants in ABCB6 and GDF3 were identified with incomplete penetrance, highlighting the complex inheritance pattern associated with this phenotype. In the coloboma/microphthalmia patients, four other variants were identified in CYP1B1, and CYP1B1 emerged as a candidate gene to be considered as a modifier in coloboma/ microphthalmia.

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Section: Discussionmentioning

confidence: 99%

Exome sequencing in developmental eye disease leads to identification of causal variants in GJA8, CRYGC, PAX6 and CYP1B1

et al. 2013

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“…In a study of a child with bilateral anophthalmia, it was discovered that the Sox2 gene lies with the intron of an ncRNA, which was named Sox2 overlapping transcript (Sox2OT) (Fantes et al, 2003) just as the Dlx6 gene lies within an intron of the ncRNA Evf-2 (Feng et al, 2006). In contrast to OSTs, Sox2OT is transcribed from the same strand as Sox2 and splices around its partnered protein coding gene.…”

Section: Sox2otmentioning

confidence: 99%

New meaning in the message: Noncoding RNAs and their role in retinal development

Rapicavoli

Blackshaw

2009

Developmental Dynamics

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Recent studies have indicated that non-protein-coding RNAs (ncRNAs) may play prominent and diverse roles in the development of the nervous system. These ncRNAs are now known to perform a broad range of cellular functions, and in particular appear to be prominent players in the regulation of transcription and translation. In this review, we discuss recent advances in our understanding of the role of ncRNAs in vertebrate retinal development. Noncoding RNAs that are known or suspected to play a functional role in the specification and maturation of retinal cell subtypes include miRNAs, long noncoding opposite-strand transcripts (OSTs), and other long ncRNAs such as Tug1 and RNCR2. Though the mechanism of action of most of these ncRNAs is still largely unclear, it is likely that these molecules represent a major, and thus far largely unappreciated, component of the molecular machinery involved in retinal cell fate specification.

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“…These include genes principally involved in ocular development, such as CHX10, many of which are involved in the development of substructures within the eye 19,21 and genes that are involved in eye and brain development including SOX2, OTX2, and PAX6. 20,[22][23][24][25][26] Several syndromic genes are involved in developing other organs in addition to the eye, including CHD7, the gene for CHARGE syndrome 27,28 and PTCH, the gene for Gorlin syndrome. 29 There is a complex interplay between the different eye development gene pathways, which allows their expression to be finely regulated 5,27,30 and begins to explain why there is such an overlap of the phenotypes associated with mutations of each gene.…”

Section: Aetiology and Geneticsmentioning

confidence: 99%