Mutation in thePAX6 gene in twenty patients with aniridia

Chao, L; Huff, Vicki; Strong, Louise C.; Saunders, Grady F.

doi:10.1002/(sici)1098-1004(200004)15:4<332::aid-humu5>3.0.co;2-1

Cited by 42 publications

(28 citation statements)

References 38 publications

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“…3,4 Not surprisingly hot spots of mutations are constituted by CpG sites. The Arginine of codon 240 and 317 are to date the most recurrent point mutations found in the PAX6 gene according to the classical deamination of methylated Cytosine mechanism, as 29 families carry one of these two nonsense mutations 28 (PAX6 mutations database).…”

Section: Discussionmentioning

confidence: 99%

“…A small number of the patients have WAGR syndrome (Wilms tumour, aniridia, genitourinary anomalies, mental retardation), a contiguous gene syndrome arising from deletion of chromosome 11p13, which encompasses both the PAX6 and WT1 genes. 3,4 The aniridia gene (AN) has been localised on chromosome 11p13 5 -9 and isolated by positional cloning. 10 PAX6 gene spans 22 kilobases, is divided into 14 exons and encodes by alternative splicing two proteins of 422 and 436 amino acids.…”

Section: Introductionmentioning

confidence: 99%

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Screening for PAX6 gene mutations is consistent with haploinsufficiency as the main mechanism leading to various ocular defects

et al. 2003

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PAX6, a paired box transcriptional factor, is considered as the master control gene for morphogenesis of the eye. Human PAX6 mutations have been associated with a range of eye abnormalities, including aniridia, various anterior segment defects and foveal hypoplasia. We carried out a mutational analysis of the PAX6 gene in 54 unrelated patients with aniridia or related syndromes. A deleterious variation was evidenced in 17 sporadic cases (50%) and in 13 (72%) familial cases. Twenty-four different mutations, 17 of which are novel, were found. The spectrum of PAX6 mutations was highly homogeneous: 23 mutations (96%) leading to premature stop codons (eight nonsense and four splice site mutations, 11 insertions and deletions) and only one (4%) missense mutation. Twenty-two mutations were associated with aniridia phenotypes whereas two were associated with atypical phenotypes. These latter encompassed a missense mutation (R19P) in an individual with a microphthalmia-sclerocornea and a splice site mutation (IVS4+5G4C) in a family presenting with a congenital nystagmus. Both represented the most probably hypomorphic alleles. Aniridia cases were associated with nonsense or frameshifting mutations. A careful examination of the phenotypes did not make it possible to recognise significant differences whenever the predicted protein was deprived of one or another of its functional domains. This strongly suggested that most of the truncating mutations generated null alleles by nonsense mediated mRNA decay. Our observations support the concept of dosage effects of the PAX6 mutations as well as presenting evidence for variable expressivity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Screening for PAX6 gene mutations is consistent with haploinsufficiency as the main mechanism leading to various ocular defects

et al. 2003

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“…It is known that PAX6 missense mutations may give rise to variant phenotypes and most of them are clustered in the highly conserved residues of the PRD. 4,5,[10][11][12][13][14][15] In contrast, very few missense mutations have been found in the HD region. 4,5 Mutation p.S216P was the fourth mutation identified in the HD region.…”

Section: Discussionmentioning

confidence: 99%

“…The mutations are either intragenic mutations or large deletions in the region of the PAX6 gene. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] To date, more than 300 intragenic mutations of the PAX6 have been described. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Most of these mutations are nonsense mutations, frame-shifting insertions or deletion, and splicing mutations, which directly or indirectly introduce premature termination codons (PTCs), and are predominantly associated with AN.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 In contrast, missense mutations usually generate distinctive non-AN phenotypes, including anterior segment anomalies, isolated forveal hypoplasia, and optic nerve malformations. 4,5,[10][11][12][13][14][15] Peters anomaly is a rare disorder characterized by congenital central corneal opacity and variable degrees of iridolenticulocorneal adhesions. The corneal opacity is usually associated with defects in corneal endothelium, Descemet's member, and posterior stroma.…”

Section: Introductionmentioning

confidence: 99%

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Two novel mutations of the PAX6 gene causing different phenotype in a cohort of Chinese patients

Zhang

Tong

et al. 2011

Eye

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Purpose Aniridia (AN) is a rare congenital panocular disorder caused by the mutations of the paired box homeotic gene 6 (PAX6) gene. The PAX6 gene is also involved in other anterior segment malformations including Peters anomaly. We studied the PAX6 gene mutations in a cohort of affected individuals with different clinical phenotype including AN, coloboma of iris and choroid, or anterior segment malformations. Patients and methods Six unrelated families and 10 sporadic patients were examined clinically. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Mutation screening of all exons of the PAX6 gene was performed by direct sequencing of PCR-amplified DNA fragments. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect large deletions.Results By clinical examination, the patients and the pedigrees were divided into the following three groups: AN, coloboma of iris and choroids, and the anterior segment malformations including peters anomaly. Sequencing of the PAX6 gene, three intragenic mutations including a novel heterozygous splicing-site mutations c.357-3C4G (p.Ser119fsX) were identified in the patients of the AN group. A novel missense mutation c.643T4C (p.S216P) was detected in the anterior segment malformation group. The mutation p.S216P located in the homeodomain region of the PAX6 caused the phenotype of Peters anomaly in family A6 with different expressing. Through MLPA analysis, a large deletion including the whole PAX6 gene and DKFZ p686k1684 gene was detected in one sporadic patient from the AN group. Neither intragenic mutation nor large deletion was identified in the group with coloboma of iris and choroid. Conclusion Our findings further confirmed that different kind of mutations might cause different ocular phenotype, and clearly clinical phenotype classification might increase the mutation detection rate of the PAX6 gene.

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Third case of WAGR syndrome with severe obesity and constitutional deletion of chromosome (11)(p12p14)

Gül¹,

Oğur²,

Tunca³

et al. 2002

Am. J. Med. Genet.

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Mutation in thePAX6 gene in twenty patients with aniridia

Cited by 42 publications

References 38 publications

Screening for PAX6 gene mutations is consistent with haploinsufficiency as the main mechanism leading to various ocular defects

Screening for PAX6 gene mutations is consistent with haploinsufficiency as the main mechanism leading to various ocular defects

Two novel mutations of the PAX6 gene causing different phenotype in a cohort of Chinese patients

Third case of WAGR syndrome with severe obesity and constitutional deletion of chromosome (11)(p12p14)

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