A homozygote variant in the tRNA splicing endonuclease subunit 54 causes pontocerebellar hypoplasia in a consanguineous Iranian family

Sepahvand, Afrooz; Razmara, Ehsan; Bitarafan, Fatemeh; Galehdari, Mohammad; Tavasoli, Ali Reza; Almadani, Navid; Garshasbi, Masoud

doi:10.1002/mgg3.1413

Cited by 6 publications

(2 citation statements)

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“…III.1, III.4, III.6, III.8 and III.12) and also two healthy members (II.4 and III.11) within the family were subjected to paired‐end WES using Illumina HiSeq 4000 platform to a mean per‐sample depth of 100×. The procedure and filtering steps were carried out according to the previous studies 22,28,29 …”

Section: Methodsmentioning

confidence: 99%

“…The procedure and filtering steps were carried out according to the previous studies. 22,28,29 Raw reads in Fastq format from the exome sequencing were aligned to the hg19 reference genome downloaded from UCSC 30 with Burrows-Wheeler Aligner (BWA). 31 The PCR duplicates were removed using the Sequence Alignment/Map (SAM) format (SAMtools-0.1.16) 32 and aligned reads were processed with the Count Covariates, Table Recalibration, Realigner Target Creator, Indel Realigner step with GenomeAnalysisTK-1.4.…”

Section: Whole-exome Sequencing (Wes) and Linkage Analysismentioning

confidence: 99%

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A biallelic variant in POLR2C is associated with congenital hearing loss and male infertility: Case report

Bitarafan

Razmara

Jafarinia

et al. 2023

Eur J Clin Investigation

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Background: DNA-directed RNA polymerase II subunit 3 (RPB3) is the third largest subunit of RNA polymerase II and is encoded by the POLR2C (OMIM:180663).A large Iranian family with congenital hearing loss and infertility is described here with genetic and clinical characterizations of five male patients. Methods: After doing clinical examinations, the proband was subjected to karyotyping and GJB2/6 sequencing to rule out the most evident chromosomal and gene abnormalities for male infertility and hearing loss, respectively. A customdesigned next-generation sequencing panel was also used to detect mutations in deafness-related genes. Finally, to reveal the underlying molecular cause(s) justifying hearing loss and male infertility, five male patients and 2 healthy male controls within the family were subjected to paired-end whole-exome sequencing (WES). Linkage analysis was also performed based on the data. Results:All male patients showed prelingual sensorineural hearing loss and also decreased sperm motility. Linkage analysis determined 16q21 as the most susceptible locus in which a missense variant in exon 7 of POLR2C-NM_032940.3:c.545T>C;p.(Val182Ala)-was identified as a 'likely pathogenic' variant co-segregated with phenotypes.Conclusions: Using segregation and in silico analyses, for the first time, we suggested that the NM_032940.3:c.545T>C; p.(Val182Ala) in POLR2C is associated with hearing loss and male infertility.

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Section: Methodsmentioning

confidence: 99%