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基于 smMIPs 的有效测序在英国斯特格病病例和相关黄斑病变相关基因中的应用。

Effective smMIPs-Based Sequencing of Maculopathy-Associated Genes in Stargardt Disease Cases and Allied Maculopathies from the UK.

机构信息

Leeds Institute of Medical Research, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK.

Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

出版信息

Genes (Basel). 2023 Jan 11;14(1):191. doi: 10.3390/genes14010191.


DOI:10.3390/genes14010191
PMID:36672932
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9859292/
Abstract

Macular dystrophies are a group of individually rare but collectively common inherited retinal dystrophies characterised by central vision loss and loss of visual acuity. Single molecule Molecular Inversion Probes (smMIPs) have proved effective in identifying genetic variants causing macular dystrophy. Here, a previously established smMIPs panel tailored for genes associated with macular diseases has been used to examine 57 UK macular dystrophy cases, achieving a high solve rate of 63.2% (36/57). Among 27 bi-allelic STGD1 cases, only three novel variants were identified, illustrating that the majority of variants in Caucasian STGD1 cases are currently known. We examined cases with -associated disease in detail, comparing our results with a previously reported variant grading system, and found this model to be accurate and clinically useful. In this study, we showed that -associated disease could be distinguished from other forms of macular dystrophy based on clinical evaluation in the majority of cases (34/36).

摘要

黄斑营养不良是一组罕见但又常见的遗传性视网膜疾病,其特征是中心视力丧失和视力下降。单分子分子反转探针 (smMIPs) 已被证明可有效识别导致黄斑营养不良的遗传变异。在这里,我们使用了一个先前建立的针对与黄斑疾病相关基因的 smMIPs 小组,对 57 例英国黄斑营养不良病例进行了检测,其解决率高达 63.2%(36/57)。在 27 例双等位基因 STGD1 病例中,仅鉴定出 3 个新的变异,这表明在白种人 STGD1 病例中,大多数变异目前已经知晓。我们详细检查了与相关疾病的病例,将我们的结果与先前报道的变异分级系统进行了比较,发现该模型准确且在临床上有用。在这项研究中,我们表明在大多数情况下(34/36),基于临床评估可以区分与疾病相关的疾病和其他形式的黄斑营养不良。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65be/9859292/d47648123bd0/genes-14-00191-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65be/9859292/d47648123bd0/genes-14-00191-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65be/9859292/d47648123bd0/genes-14-00191-g001.jpg

相似文献

[1]
Effective smMIPs-Based Sequencing of Maculopathy-Associated Genes in Stargardt Disease Cases and Allied Maculopathies from the UK.

Genes (Basel). 2023-1-11

[2]
Cost-effective molecular inversion probe-based ABCA4 sequencing reveals deep-intronic variants in Stargardt disease.

Hum Mutat. 2019-6-18

[3]
Genotypes Predispose Phenotypes-Clinical Features and Genetic Spectrum of -Associated Retinal Dystrophies.

Genes (Basel). 2020-11-27

[4]
Targeted sequencing and in vitro splice assays shed light on ABCA4-associated retinopathies missing heritability.

HGG Adv. 2023-10-12

[5]
Using single molecule Molecular Inversion Probes as a cost-effective, high-throughput sequencing approach to target all genes and loci associated with macular diseases.

Hum Mutat. 2022-12

[6]
ABCA4-Associated Stargardt Disease.

Klin Monbl Augenheilkd. 2020-3

[7]
The genetic architecture of Stargardt macular dystrophy (STGD1): a longitudinal 40-year study in a genetic isolate.

Eur J Hum Genet. 2020-7

[8]
Extremely hypomorphic and severe deep intronic variants in the locus result in varying Stargardt disease phenotypes.

Cold Spring Harb Mol Case Stud. 2018-8-1

[9]
Targeted next-generation sequencing identifies ABCA4 mutations in Chinese families with childhood-onset and adult-onset Stargardt disease.

Biosci Rep. 2021-6-25

[10]
Novel variants of ABCA4 in Han Chinese families with Stargardt disease.

BMC Med Genet. 2020-10-31

引用本文的文献

[1]
Genetic Screening of a Nonsyndromic Amelogenesis Imperfecta Patient Cohort Using a Custom smMIP Reagent for Selective Enrichment of Target Loci.

Hum Mutat. 2025-7-22

[2]
How to Set Up Genetic Counselling for Inherited Macular Dystrophies: Focus on Genetic Characterization.

Int J Mol Sci. 2023-6-3

本文引用的文献

[1]
Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis.

Front Cell Dev Biol. 2023-2-3

[2]
Using single molecule Molecular Inversion Probes as a cost-effective, high-throughput sequencing approach to target all genes and loci associated with macular diseases.

Hum Mutat. 2022-12

[3]
Personalized genetic counseling for Stargardt disease: Offspring risk estimates based on variant severity.

Am J Hum Genet. 2022-3-3

[4]
Next-Generation Sequencing Applications for Inherited Retinal Diseases.

Int J Mol Sci. 2021-5-26

[5]
Target 5000: a standardized all-Ireland pathway for the diagnosis and management of inherited retinal degenerations.

Orphanet J Rare Dis. 2021-5-5

[6]
Panel-based genetic testing for inherited retinal disease screening 176 genes.

Mol Genet Genomic Med. 2021-12

[7]
Whole-exome sequencing in 168 Korean patients with inherited retinal degeneration.

BMC Med Genomics. 2021-3-10

[8]
Resolving the dark matter of ABCA4 for 1054 Stargardt disease probands through integrated genomics and transcriptomics.

Genet Med. 2020-7

[9]
Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations.

Prog Retin Eye Res. 2020-11

[10]
Characterizing the pharmacogenome using molecular inversion probes for targeted next-generation sequencing.

Pharmacogenomics. 2019-9

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