Frequency of Epidermal Growth Factor Receptor Gene Variant in Roma Population.

Aims: The pathogenic variant, p.GLY428Asp (c.1283G-A), in the epidermal growth factor receptor (EGFR) gene causes neonatal inflammatory skin and bowel disease 2, a disorder that is lethal during infancy due to skin infections and sepsis. This variant seems to be restricted to people of Roma origin with the majority of patients thus far reported being from Slovakia or the Czech Republic. The aim of this study was to establish the frequency of this variant in the Roma population in Slovakia. Methods: A population sample of 1321 unrelated healthy individuals of Roma origin from Slovakia was tested for the p.GLY428Asp variant in EGFR gene by real-time PCR. Results: The carrier frequency in the Roma ethnic group was 2.65%. Conclusions: This is the first report of the frequency of this variant. A high frequency of carriers together with a significant number of patients reported previously proves the p.GLY428Asp variant in the EGFR gene is a major health concern of the Roma populations in Slovakia and neighboring regions.

UFM1 founder mutation in the Roma population causes recessive variant of H-ABC.

OBJECTIVE: To identify the gene defect in patients with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) who are negative for TUBB4A mutations. METHODS: We performed homozygosity mapping and whole exome sequencing (WES) to detect the disease-causing variant. We used a Taqman assay for population screening. We developed a luciferase reporter construct to investigate the effect of the promoter mutation on expression. RESULTS: Sixteen patients from 14 families from different countries fulfilling the MRI criteria for H-ABC exhibited a similar, severe clinical phenotype, including lack of development and a severe epileptic encephalopathy. The majority of patients had a known Roma ethnic background. Single nucleotide polymorphism array analysis in 5 patients identified one large overlapping homozygous region on chromosome 13. WES in 2 patients revealed a homozygous deletion in the promoter region of UFM1. Sanger sequencing confirmed homozygosity for this variant in all 16 patients. All patients shared a common haplotype, indicative of a founder effect. Screening of 1,000 controls from different European Roma panels demonstrated an overall carrier rate of the mutation of 3%-25%. Transfection assays showed that the deletion significantly reduced expression in specific CNS cell lines. CONCLUSIONS: UFM1 encodes ubiquitin-fold modifier 1 (UFM1), a member of the ubiquitin-like family involved in posttranslational modification of proteins. Its exact biological role is unclear. This study associates a UFM1 gene defect with a disease and sheds new light on possible UFM1 functional networks.

Analysis of SCN5A Gene Variants in East Slovak Patients with Cardiomyopathy.

OBJECTIVE: Mutations in ion channels genes are potential cause of cardiomyopathy. The SCN5A gene (sodium channel, voltage gated, type V alpha subunit gene; 3p21) belongs to the family of cardiac sodium channel genes. Mutations in SCN5A gene lead to decreased Na+ current and ion unbalance. The SCN5A gene mutations are found in approximately 2% of patients with dilated cardiomyopathy (DCM), and they may be potential phenotype modifiers in hypertrophic cardiomyopathy (HCM). The role of SCN5A gene mutations in cardiomyopathy is not fully elucidated. METHODS: Three selected exons (12, 20, and 21) of the SCN5A gene in the cohort of 58 East Slovak patients with dilated and HCM were analyzed by the Sanger sequencing method in order to detect etiopathogenic mutations associated with dilated and HCM. RESULTS: The mutation screening of three selected exons of SCN5A gene in the cohort of 27 DCM, 12 HCM patients, and 16 controls identified 10 missense genetic variants. Three of them (T1247I, A1260D, and G1262S), all in exon 21 of the SCN5A gene, were potentially damaging and disease-causing variants. CONCLUSION: Data from this study demonstrate that SCN5A gene variants have important role in the etiopathogenesis of dilated and HCM.