دورية أكاديمية

Genetic and Clinical Analyses of the KIZ-c.226C>T Variant Resulting in a Dual Mutational Mechanism

التفاصيل البيبلوغرافية
العنوان: Genetic and Clinical Analyses of the KIZ-c.226C>T Variant Resulting in a Dual Mutational Mechanism
المؤلفون: Yogapriya Sundaresan, Antonio Rivera, Alexey Obolensky, Prakadeeswari Gopalakrishnan, Hanit Ohayon Hadad, Aya Shemesh, Samer Khateb, Maya Ross, Ron Ofri, Sharon Durst, Hadas Newman, Rina Leibu, Shiri Soudry, Dinah Zur, Tamar Ben-Yosef, Eyal Banin, Dror Sharon
المصدر: Genes, Vol 15, Iss 6, p 804 (2024)
بيانات النشر: MDPI AG, 2024.
سنة النشر: 2024
المجموعة: LCC:Genetics
مصطلحات موضوعية: clinical manifestation, exonic sequence enhancer, gene expression, retinal disease, Genetics, QH426-470
الوصف: Retinitis pigmentosa (RP) is a heterogeneous inherited retinal disorder. Mutations in KIZ cause autosomal recessive (AR) RP. We aimed to characterize the genotype, expression pattern, and phenotype in a large cohort of KIZ cases. Sanger and whole exome sequencing were used to identify the KIZ variants. Medical records were reviewed and analyzed. Thirty-one patients with biallelic KIZ mutations were identified: 28 homozygous for c.226C>T (p.R76*), 2 compound heterozygous for p.R76* and c.3G>A (p.M1?), and one homozygous for c.247C>T (p.R83*). c.226C>T is a founder mutation among patients of Jewish descent. The clinical parameters were less severe in KIZ compared to DHDDS and FAM161A cases. RT-PCR analysis in fibroblast cells revealed the presence of four different transcripts in both WT and mutant samples with a lower percentage of the WT transcript in patients. Sequence analysis identified an exonic sequence enhancer (ESE) that includes the c.226 position which is affected by the mutation. KIZ mutations are an uncommon cause of IRD worldwide but are not rare among Ashkenazi Jews. Our data indicate that p.R76* affect an ESE which in turn results in the pronounced skipping of exon 3. Therefore, RNA-based therapies might show low efficacy since the mutant transcripts are spliced.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2073-4425
العلاقة: https://www.mdpi.com/2073-4425/15/6/804Test; https://doaj.org/toc/2073-4425Test
DOI: 10.3390/genes15060804
الوصول الحر: https://doaj.org/article/586c2808fa8c4ba4aec928c15384719dTest
رقم الانضمام: edsdoj.586c2808fa8c4ba4aec928c15384719d
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20734425
DOI:10.3390/genes15060804