A novel variant of ST3GAL3 causes non‐syndromic autosomal recessive intellectual disability in Iranian patients

Abstract

Background: The number of reported genes causing non-syndromic autosomal recessive intellectual disability (NS-ARID) is increasing. For example, mutations in the ST3GAL3 gene have been reported to be associated with NS-ARID. In the present study, we aimed to determine the genetic cause of the NS-ARID in a five-generation consanguineous Iranian family. Methods: We subjected four patients with an initial diagnosis of NS-ID in an Iranian family. To identify the possible genetic cause(s), whole-exome sequencing was performed on the proband and Sanger sequencing was applied to investigate cosegregation analysis. Using in silico predictive tools, the possible impacts of the variant on the structure and function of ST3Gal-III were predicted. Results: The common clinical features were detected in all affected members who were suffering from a severe ID. Using whole-exome sequencing, a novel variant, c.704C>T or p.(Thr235Met), in exon 9 of the ST3GAL3 gene (NM_001270461.2, OMIM# 606494) was identified and verified by Sanger sequencing. This variant is located next to the VS motif of ST3Gal-III, which is a vital part of the catalytical domains. Conclusions: In the present study, we identified a novel missense variant, c.704C>T or p.(Thr235Met), in the ST3GAL3. To our knowledge, is the third variant in this gene to be associated with NS-ARID. Our findings highlight the need for further investigations into the mechanisms by which variants in ST3GAL3 contribute to neurological dysfunction.

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

“…Additionally, the patients were screened for neurodevelopmental disorders, hypotonia and intellectual and behavioural abnormalities in accordance with the criteria provided previously 22 …”

“…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 …”

“…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.…”

ACER3-Realted Leukoencephalopathy: Expanding The Clinical and Imaging Findings Spectrum Due to Novel Variants

“…High-throughput sequencing was performed for each captured library on Illumina's HiSeq4000 instrument in accordance with the manufacturer's protocols (Illumina Inc, USA). Analysis of Exome data has been described before in detail (13). In summary, raw reads in FASTQ format were initially aligned onto the hg19 reference genome using BWA 0.7.17 after ensuring the elimination of low-quality reads.…”

The epilepsy phenotype of ST3GAL3‐related developmental and epileptic encephalopathy

“…1,4 There are a growing number of rare autosomal recessive genes that may result in DEE phenotypes, one of which includes biallelic variants in ST3GAL3. [5][6][7][8][9][10] The ST3GAL3 gene encodes for the Golgi membrane enzyme, beta-galactosidase-alpha-2,3 sialytransferase-III (ST3GAL3), which is highly expressed in the developing brain. 1,[10][11][12][13] ST3GAL3 is involved in the formation of sialyl epitopes on glycoproteins, which help to determine the functional specificity of glycans, and are also important in brain function and development.…”