Mutations in the SPARC-Related Modular Calcium-Binding Protein 1 Gene, SMOC1, Cause Waardenburg Anophthalmia Syndrome

Abouzeid, Hana; Boisset, Gaëlle; Favez, Tatiana; Youssef, Mohamed A.; Marzouk, Iman; Shakankiry, Nihal El; Bayoumi, Nader; Descombes, Patrick; Agosti, C.; Munier, Francis L.; Schorderet, Daniel F.

doi:10.1016/j.ajhg.2010.12.002

Cited by 69 publications

(59 citation statements)

References 38 publications

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“…Recently, three groups used autozygosity/homozygosity mapping to narrow the locus for WAS to a 1–3 Mb interval at chromosome 14q24.2 [74, 76, 77]. All three researchers found mutations in the secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding 1 ( SMOC1 ) gene that were predicted to cause loss of function [74, 76, 77].…”

Section: Introductionmentioning

confidence: 99%

“…All three researchers found mutations in the secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding 1 ( SMOC1 ) gene that were predicted to cause loss of function [74, 76, 77]. Mutations have so far been identified in 12 families, with evidence of genetic heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

“…Examination of the hindlimbs of these mutant mice showed strain dependent synostosis between the fourth and fifth metatarsals, syndactyly and pes valgus, bowed tibiae and hypoplastic fibulae and soft tissue syndactyly in the forelimbs [76]. Expression in Danio rerio included the choroid fissure, brain and pharyngeal arches [77] and targeting of the Danio rerio SMOC1 orthologue with antisense morpholinos caused microphthalmia, coloboma with delayed closure of the choroid fissure, defects of the forebrain and possibly the pharyngeal arches [77]. …”

Section: Introductionmentioning

confidence: 99%

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Eye development genes and known syndromes

Slavotinek

2011

Molecular Genetics and Metabolism

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Anophthalmia and microphthalmia (A/M) are significant eye defects because they can have profound effects on visual acuity. A/M is associated with non-ocular abnormalities in an estimated 33–95% of cases and around 25% of patients have an underlying genetic syndrome that is diagnosable. Syndrome recognition is important for targeted molecular genetic testing, prognosis and for counseling regarding recurrence risks. This review provides clinical and molecular information for several of the commonest syndromes associated with A/M: Anophthalmia-Esophageal-Genital syndrome, caused by SOX2 mutations, Anophthalmia and pituitary abnormalities caused by OTX2 mutations, Matthew-Wood syndrome caused by STRA6 mutations, Oculocardiafaciodental syndrome and Lenz microphthalmia caused by BCOR mutations, Microphthalmia Linear Skin pigmentation syndrome caused by HCCS mutations, Anophthalmia, pituitary abnormalities, polysyndactyly caused by BMP4 mutations and Waardenburg anophthalmia caused by mutations in SMOC1. In addition, we briefly discuss the ocular and extraocular phenotypes associated with several other important eye developmental genes, including GDF6, VSX2, RAX, SHH, SIX6 and PAX6.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Eye development genes and known syndromes

Slavotinek

2011

Molecular Genetics and Metabolism

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“…Cases of anophthalmia and microphthalmia have been associated with homozygous and heterozygous mutations in genes at the core of forebrain regulatory networks (Beccari et al, 2013), such as the transcription factors (TFs) SOX2 (Fantes et al, 2003), OTX2 (Ragge et al, 2005), PAX6 (Glaser et al, 1994), VSX2 (CHX10) (Ferda Percin et al, 2000), RAX (Voronina et al, 2004), FOXE3 (Reis et al, 2010) and perhaps SIX6 (Gallardo et al, 2004); in key components of cell to cell communication, including SHH (Schimmenti et al, 2003) and BMP4 (Reis et al, 2011); or in genes involved in retinal progenitor proliferation and survival such as STRA6 (Pasutto et al, 2007;White et al, 2008), BCOR (Ng et al, 2004), HCCS (Indrieri et al, 2013;Morleo et al, 2005) and SMOC1 (Abouzeid et al, 2011;Okada et al, 2011). Yet, only a minor proportion of patients receive an accurate molecular diagnosis of the pathogenesis of their ocular malformation Williamson and FitzPatrick, 2014), indicating that additional causative genes need to be identified.…”

Section: Introductionmentioning

confidence: 99%

Meis1 coordinates a network of genes implicated in eye development and microphthalmia

et al. 2015

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Microphthalmos is a rare congenital anomaly characterized by reduced eye size and visual deficits of variable degree. Sporadic and hereditary microphthalmos have been associated with heterozygous mutations in genes fundamental for eye development. Yet, many cases are idiopathic or await the identification of molecular causes. Here we show that haploinsufficiency of Meis1, which encodes a transcription factor with evolutionarily conserved expression in the embryonic trunk, brain and sensory organs, including the eye, causes microphthalmic traits and visual impairment in adult mice. By combining analysis of Meis1 loss-offunction and conditional Meis1 functional rescue with ChIP-seq and RNA-seq approaches we show that, in contrast to its preferential association with Hox-Pbx BSs in the trunk, Meis1 binds to Hox/Pbxindependent sites during optic cup development. In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components of the Notch signaling pathway. In addition, Meis1 is required for eye patterning by controlling a set of eye territory-specific transcription factors, so that in Meis1 −/− embryos boundaries among the different eye territories are shifted or blurred. We propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations.

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“…This approach has been implemented in two recent studies which identified homozygous mutations in SMOC1, encoding Sparc-related modular calcium-binding protein 1 (SMOC1), as a cause of the rare autosomal recessive Waardenburg anophthalmia syndrome (WAS) [83,84], a finding also reported in another study [85]. WAS is also known as ophthalmo-acromelic syndrome affecting development of the eyes (anophthalmia, microphthalmia) and limbs (post-axial oligodactyly, syndactyly).…”

Section: Mouse Models Generated By Insertional and Enu-induced Mutagementioning

confidence: 95%

The Mouse as a Developmental Model for Cleft Lip and Palate Research

Gritli-Linde¹

2012

Frontiers of Oral Biology

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Vertebrate and invertebrate model organisms are essential for deciphering biological processes. One of these, the mouse, proved to be a valuable model for understanding the etiopathogenesis of a vast array of human diseases, including congenital malformations such as orofacial clefting conditions. This small mammal's usefulness in cleft lip and palate research stems not only from the striking anatomical and molecular similarities of lip and palate development between human and mouse embryos, but also from its amenability to experimental and genetic manipulation. Using some recent studies as illustrative examples, this review describes different ways of generating and exploiting mouse models to study normal and abnormal development of the lip and palate. Despite a few surmountable disadvantages of using the mouse, numerous mutants have revealed a growing number of molecular key players and have pointed at a tight and complex molecular control during each step of lip and palate development.

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Mutations in the SPARC-Related Modular Calcium-Binding Protein 1 Gene, SMOC1, Cause Waardenburg Anophthalmia Syndrome

Cited by 69 publications

References 38 publications

Eye development genes and known syndromes

Eye development genes and known syndromes

Meis1 coordinates a network of genes implicated in eye development and microphthalmia

The Mouse as a Developmental Model for Cleft Lip and Palate Research

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