Browsing by Author "Taurina, Gita"

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    GJB1 Gene Analysis in Two Extended Families with X-Linked Charcot-Marie-Tooth Disease
    (2021-06-23) Kovale, Sabine; Terauda, Ruta; Millere, Elina; Taurina, Gita; Murmane, Daiga; Isakova, Jekaterina; Kenina, Viktorija; Gailite, Linda; Scientific Laboratory of Molecular Genetics
    X-linked Charcot-Marie-Tooth (CMT) disease type I (CMTX1) is the second most frequent type of CMT disease caused by pathogenic variants in the GJB1 gene. We described 2 extended cases (families) with CMTX1 with identified pathogenic variants - p.Val139Met and p.Arg215Trp. In both the families, neurological symptoms started earlier in male than in female patients. In some family members, molecular diagnostics was performed prior to neurological investigation due to family cascade screening. There was variable neurological phenotype representing CMT. Conclusions: There is a large clinical heterogeneity in CMTX, even amongst the family members.
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    Overview of Neuromuscular Disorder Molecular Diagnostic Experience for the Population of Latvia
    (2022-06-16) Lace, Baiba; Micule, Ieva; Kenina, Viktorija; Setlere, Signe; Strautmanis, Jurgis; Kazaine, Inese; Taurina, Gita; Murmane, Daiga; Grinfelde, Ieva; Kornejeva, Liene; Krumina, Zita; Sterna, Olga; Radovica-Spalvina, Ilze; Vasiljeva, Inta; Gailite, Linda; Stavusis, Janis; Livcane, Diana; Kidere, Dita; Malniece, Ieva; Inashkina, Inna; Rīga Stradiņš University; Scientific Laboratory of Molecular Genetics
    Background and ObjectivesGenetic testing has become an integral part of health care, allowing the confirmation of thousands of hereditary diseases, including neuromuscular disorders (NMDs). The reported average prevalence of individual inherited NMDs is 3.7-4.99 per 10,000. This number varies greatly in the selected populations after applying population-wide studies. The aim of this study was to evaluate the effect of genetic analysis as the first-tier test in patients with NMD and to calculate the disease prevalence and allelic frequencies for reoccurring genetic variants.MethodsPatients with NMD from Latvia with molecular tests confirming their diagnosis in 2008-2020 were included in this retrospective study.ResultsDiagnosis was confirmed in 153 unique cases of all persons tested. Next-generation sequencing resulted in a detection rate of 37%. Two of the most common childhood-onset NMDs in our population were spinal muscular atrophy and dystrophinopathies, with a birth prevalence of 1.01 per 10,000 newborns and 2.08 per 10,000 (male newborn population), respectively. The calculated point prevalence was 0.079 per 10,000 for facioscapulohumeral muscular dystrophy type 1, 0.078 per 10,000 for limb-girdle muscular dystrophy, 0.073 per 10,000 for nondystrophic congenital myotonia, 0.052 per 10,000 for spinobulbar muscular atrophy, and 0.047 per 10,000 for type 1 myotonic dystrophy.DiscussionDNA diagnostics is a successful approach. The carrier frequencies of the common CAPN3, FKRP, SPG11, and HINT1 gene variants as well as that of the SMN1 gene exon 7 deletion in the population of Latvia are comparable with data from Europe. The carrier frequency of the CLCN1 gene variant c.2680C>T p.(Arg894Ter) is 2.11%, and consequently, congenital myotonia is the most frequent NMD in our population.
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    Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes
    (2024-03) Hitti-Malin, Rebekkah J.; Panneman, Daan M.; Corradi, Zelia; Boonen, Erica G.M.; Astuti, Galuh; Dhaenens, Claire Marie; Stöhr, Heidi; Weber, Bernhard H.F.; Sharon, Dror; Banin, Eyal; Karali, Marianthi; Banfi, Sandro; Ben-Yosef, Tamar; Glavač, Damjan; Farrar, G. Jane; Ayuso, Carmen; Liskova, Petra; Dudakova, Lubica; Vajter, Marie; Ołdak, Monika; Szaflik, Jacek P.; Matynia, Anna; Gorin, Michael B.; Kämpjärvi, Kati; Bauwens, Miriam; De Baere, Elfride; Hoyng, Carel B.; Li, Catherina H.Z.; Klaver, Caroline C.W.; Inglehearn, Chris F.; Fujinami, Kaoru; Rivolta, Carlo; Allikmets, Rando; Zernant, Jana; Lee, Winston; Podhajcer, Osvaldo L.; Fakin, Ana; Sajovic, Jana; AlTalbishi, Alaa; Valeiņa, Sandra; Taurina, Gita; Vincent, Andrea L.; Roberts, Lisa; Ramesar, Raj; Sartor, Giovanna; Luppi, Elena; Downes, Susan M.; van den Born, L. Ingeborgh; McLaren, Terri L.; De Roach, John N.; Lamey, Tina M.; Thompson, Jennifer A.; Chen, Fred K.; Tracewska, Anna M.; Kamakari, Smaragda; Sallum, Juliana Maria Ferraz; Bolz, Hanno J.; Kayserili, Hülya; Roosing, Susanne; Cremers, Frans P.M.; Department of Ophthalmology
    Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2%), PRPH2 (6.7%), CDHR1 (6.1%), PROM1 (4.3%) and RP1L1 (3.1%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1:c.783G>A and CNGB3:c.1208G>A. Notably, segregation analysis was not routinely performed for variant phasing—a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes.
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    Two Cases of Leigh Syndrome in One Family : Diagnostic Challenges and Clinical Management Experience in Latvia
    (2021) Katkevica, Arta; Kreile, Madara; Grinfelde, Ieva; Taurina, Gita; Micule, Ieva; Dzivite-Krisane, Iveta; Smite-Laguna, Arta; Malniece, Ieva; Rīga Stradiņš University
    Leigh syndrome is a neurodegenerative disorder with an incidence of 1: 40,000 live births. The clinical presentation of LS is highly variable with heterogeneity in the disease-associated symptoms of cerebellar, motor, and extrapyramidal dysfunction and common infections. There is no effective treatment for this condition; as such, the prognosis of this condition is very poor with death occurring within the first few years of life. In this study, we report the first LS case in Latvia with SURF1 pathogenic variants in two siblings. The difficulties encountered establishing a diagnosis for the first proband and the effective prenatal diagnosis for the second offspring that led to termination of the pregnancy are discussed.