The majority of autosomal recessive nanophthalmos and posterior microphthalmia can be attributed to biallelic sequence and structural variants in MFRP and PRSS56
| العنوان: | The majority of autosomal recessive nanophthalmos and posterior microphthalmia can be attributed to biallelic sequence and structural variants in MFRP and PRSS56 |
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| المؤلفون: | Basamat Almoallem, Gavin Arno, Anne Destree, Elfride De Baere, Denise Williams, Anthony T. Moore, Thomy de Ravel, Ingele Casteels, Andrew R. Webster, Sarah Hull, Irina Balikova, Bart P. Leroy, Martina Suzani, Julie De Zaeytijd, John R. Ainsworth, Hannah Verdin, Michelle Y. Peng |
| المساهمون: | Medical Genetics |
| المصدر: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) Scientific reports, vol 10, iss 1 SCIENTIFIC REPORTS |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, lcsh:Medicine, Gene mutation, PHENOTYPE, Compound heterozygosity, Microphthalmia, Cohort Studies, Exon, 0302 clinical medicine, Genotype, Medicine and Health Sciences, 2.1 Biological and endogenous factors, Microphthalmos, Aetiology, lcsh:Science, Child, Genetics, Multidisciplinary, Molecular medicine, ASSOCIATION, Middle Aged, Disease gene identification, Microphthalmos/genetics, Child, Preschool, Female, FRIZZLED-RELATED PROTEIN, Adult, Serine Proteases/genetics, Heterozygote, Adolescent, DNA Copy Number Variations, Biology, Article, 03 medical and health sciences, Clinical Research, RETINITIS-PIGMENTOSA, GENE MUTATION, Retinitis pigmentosa, medicine, Humans, Family, Allele, Membrane Proteins/genetics, Preschool, Alleles, Aged, IDENTIFICATION, Whole Genome Sequencing, HIGH HYPEROPIA, lcsh:R, Membrane Proteins, Hereditary eye disease, medicine.disease, Brain Disorders, 030104 developmental biology, Mutation, 030221 ophthalmology & optometry, FOVEOSCHISIS, lcsh:Q, Serine Proteases |
| الوصف: | This study aimed to genetically and clinically characterize a unique cohort of 25 individuals from 21 unrelated families with autosomal recessive nanophthalmos (NNO) and posterior microphthalmia (MCOP) from different ethnicities. An ophthalmological assessment in all families was followed by targeted MFRP and PRSS56 testing in 20 families and whole-genome sequencing in one family. Three families underwent homozygosity mapping using SNP arrays. Eight distinct MFRP mutations were found in 10/21 families (47.6%), five of which are novel including a deletion spanning the 5′ untranslated region and the first coding part of exon 1. Most cases harbored homozygous mutations (8/10), while a compound heterozygous and a monoallelic genotype were identified in the remaining ones (2/10). Six distinct PRSS56 mutations were found in 9/21 (42.9%) families, three of which are novel. Similarly, homozygous mutations were found in all but one, leaving 2/21 families (9.5%) without a molecular diagnosis. Clinically, all patients had reduced visual acuity, hyperopia, short axial length and crowded optic discs. Retinitis pigmentosa was observed in 5/10 (50%) of the MFRP group, papillomacular folds in 12/19 (63.2%) of MCOP and in 3/6 (50%) of NNO cases. A considerable phenotypic variability was observed, with no clear genotype-phenotype correlations. Overall, our study represents the largest NNO and MCOP cohort reported to date and provides a genetic diagnosis in 19/21 families (90.5%), including the first MFRP genomic rearrangement, offering opportunities for gene-based therapies in MFRP-associated disease. Finally, our study underscores the importance of sequence and copy number analysis of the MFRP and PRSS56 genes in MCOP and NNO. |
| وصف الملف: | application/pdf; Electronic |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6c67f6b56f74c44ecf74e0f3c5839b48Test https://pubmed.ncbi.nlm.nih.gov/31992737Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6c67f6b56f74c44ecf74e0f3c5839b48 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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