| [PMID]: | 27777502 |
| [Au] Autor: | Reis LM; Tyler RC; Weh E; Hendee KE; Kariminejad A; Abdul-Rahman O; Ben-Omran T; Manning MA; Yesilyurt A; McCarty CA; Kitchner TE; Costakos D; Semina EV |
| [Ad] Endereço: | Department of Pediatrics and Children's Research Institute at the Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, WI. |
| [Ti] Título: | Analysis of in pediatric and adult glaucoma and other ocular phenotypes. |
| [So] Source: | Mol Vis;22:1229-1238, 2016. |
| [Is] ISSN: | 1090-0535 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | PURPOSE: The gene encodes an enzyme that is a member of the cytochrome P450 superfamily. Mutations in have been mainly reported in recessive pediatric ocular phenotypes, such as primary congenital glaucoma (PCG) and congenital glaucoma with anterior segment dysgenesis (CG with ASD), with some likely pathogenic variants also identified in families affected with adult-onset primary open angle glaucoma (POAG). METHODS: We examined in 158 pediatric patients affected with PCG (eight), CG with ASD (22), CG with other developmental ocular disorders (11), juvenile glaucoma with or without additional ocular anomalies (26), and ASD or other developmental ocular conditions without glaucoma (91); in addition, a large cohort of adult patients with POAG (193) and POAG-negative controls (288) was examined. RESULTS: Recessive pathogenic variants in were identified in two PCG pedigrees, three cases with CG and ASD, and two families with CG and other ocular defects, such as sclerocornea in one patient and microphthalmia in another individual; neither sclerocornea nor microphthalmia has been previously associated with . Most of the identified causative mutations are new occurrences of previously reported pathogenic alleles with two novel variants identified: a c.1325delC, p.(Pro442Glnfs*15) frameshift allele in a family with PCG and a c.157G>A, p.(Gly53Ser) variant identified in a proband with CG, Peters anomaly, and microphthalmia. Analysis of the family history in the -positive families revealed POAG in confirmed or presumed heterozygous relatives in one family with PCG and two families with ASD/CG; POAG was associated with the c.1064_1076del, p.(Arg355Hisfs*69) allele in two of these pedigrees. Screening of an unrelated POAG cohort identified the same c.1064_1076del heterozygous allele in one individual with sporadic POAG but not in age- and ethnicity-matched POAG-negative individuals. Overall, there was no significant enrichment for mutant alleles in within the POAG cases compared to the controls. CONCLUSIONS: In summary, these data expand the mutational and phenotypic spectra of to include two novel alleles and additional developmental ocular phenotypes. The contribution of to POAG is less clear, but loss-of-function variants in , especially c.1064_1076del, p.(Arg355Hisfs*69), may be associated with an increased risk for POAG. |
| [Mh] Termos MeSH primário: |
Segmento Anterior do Olho/anormalidades
Citocromo P-450 CYP1B1/genética
Glaucoma de Ângulo Aberto/genética
Hidroftalmia/genética
Mutação
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| [Mh] Termos MeSH secundário: |
Adulto
Idoso
Idoso de 80 Anos ou mais
Alelos
Criança
Pré-Escolar
Análise Mutacional de DNA
Feminino
Seres Humanos
Masculino
Meia-Idade
Linhagem
Fenótipo
Reação em Cadeia da Polimerase
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL |
[Nm] Nome de substância:
| EC 1.14.14.1 (CYP1B1 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP1B1) |
| [Em] Mês de entrada: | 1801 |
| [Cu] Atualização por classe: | 180131 |
[Lr] Data última revisão:
| 180131 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 161026 |
| [St] Status: | MEDLINE |
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