Streamlined two-step fragment analysis PCR and exome sequencing of RFC1 for diagnostic testing of suspected CANVAS patients.

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is caused by biallelic pathogenic expansions, or compound heterozygosity with other pathogenic variants in the RFC1 gene. CANVAS is estimated to be underdiagnosed, both because of the lack of formal diagnostic criteria and molecular challenges that translate to lesser access and high cost of routine testing. Our aim was to address the need for making CANVAS genetic testing routine, by designing a streamlined two-step PCR consisting of a short-allele screening PCR and a confirmatory PCR with fragment capillary electrophoresis detection.

Preimplantation Genetic Testing within the Public Healthcare System in Slovenia.

Preimplantation genetic testing (PGT) is the earliest form of prenatal diagnosis that has become an established procedure for couples at risk of passing a severe genetic disease to their offspring. At UMC Ljubljana, we conducted a retrospective register-based study to present 15 years of PGT service within the public healthcare system in Slovenia. We collected the data of the PGT cycles from 2004 to 2019 and compared clinical outcomes for chromosomal and monogenic diseases using different embryo biopsy and testing approaches.

Evaluation of Optical Genome Mapping in Clinical Genetic Testing of Facioscapulohumeral Muscular Dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common hereditary muscular dystrophy, caused by the contraction of the D4Z4 repeats on the permissive 4qA haplotype on chromosome 4, resulting in the faulty expression of the gene. Traditional diagnostics are based on Southern blotting, a time- and effort-intensive method that can be affected by single nucleotide variants (SNV) and copy number variants (CNV), as well as by the similarity of the D4Z4 repeats located on chromosome 10. We aimed to evaluate optical genome mapping (OGM) as an alternative molecular diagnostic method for the detection of FSHD.

A novel splice-site FHOD3 founder variant is a common cause of hypertrophic cardiomyopathy in the population of the Balkans-A cohort study.

Founder variants in sarcomere protein genes account for a significant proportion of disease-causing variants in patients with hypertrophic cardiomyopathy (HCM). However, information on founder variants in non-sarcomeric protein genes, such as FHOD3, which have only recently been associated with HCM, remains scarce. In this study, we conducted a retrospective analysis of exome sequencing data of 134 probands with HCM for recurrent pathogenic variants.

Biallelic Gene Variant in Siblings With Pontocerebellar Hypoplasia, Developmental Delay, and Hearing Loss.

Background And Objectives: To report on the novel association of biallelic variant in atonal basic helix-loop-helix transcription factor 1 () gene and pontocerebellar hypoplasia (PCH), severe global developmental delay, intellectual disability, and hearing loss in a family with 2 affected siblings.

Methods: A detailed clinical assessment and exome sequencing of peripheral blood sample were performed. Segregation analysis with Sanger sequencing and structural modeling of the variant was performed to support the pathogenicity of the variant.

Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel Variant p.Glu580Lys.

Gelsolin amyloidosis typically presents with corneal lattice dystrophy and is most frequently associated with pathogenic variant p.Asp214Asn. Here we report clinical and histopathological features of gelsolin amyloidosis associated with a novel variant p.

Combination of QF-PCR and aCGH is an efficient diagnostic strategy for the detection of chromosome aberrations in recurrent miscarriage.

Background: Our aim was to conduct a comprehensive genetic evaluation using the combination of QF-PCR (quantitative fluorescence polymerase chain reaction) and aCGH (array comparative genomic hybridization) for the detection of the frequency and type of chromosome aberrations in recurrent miscarriage (RM) in the clinical setting.

Methods: This retrospective study was conducted on 73 first-trimester products of conception (POC) between September 2014 and February 2017. The POCs were collected from 73 women with at least one previous miscarriage and analyzed for chromosomal anomalies using QF-PCR and aCGH as part of the routine clinical evaluation.

Association between male infertility and genetic variability at the PON1/2 and GSTM1/T1 gene loci.

Environmental xenobiotics such as organophosphate pesticides are known factors involved in male infertility. Paraoxanase (PON) and glutathione transferase (GST) are involved in biotransformation of organophosphate pesticides. Interindividual genetic variations in biotransformation enzyme activities can lead to differences in the susceptibility to male infertility.