Overview of Neuromuscular Disorder Molecular Diagnostic Experience for the Population of Latvia

Baiba Lace; Ieva Micule; Viktorija Kenina; Signe Setlere; Jurgis Strautmanis; Inese Kazaine; Gita Taurina; Daiga Murmane; Ieva Grinfelde; Liene Kornejeva; Zita Krumina; Olga Sterna; Ilze Radovica-Spalvina; Inta Vasiljeva; Linda Gailite; Janis Stavusis; Diana Livcane; Dita Kidere; Ieva Malniece; Inna Inashkina

doi:10.1212/NXG.0000000000000685

Overview of Neuromuscular Disorder Molecular Diagnostic Experience for the Population of Latvia

Neurol Genet. 2022 May 16;8(3):e685. doi: 10.1212/NXG.0000000000000685. eCollection 2022 Jun.

Authors

Baiba Lace¹, Ieva Micule¹, Viktorija Kenina¹, Signe Setlere¹, Jurgis Strautmanis¹, Inese Kazaine¹, Gita Taurina¹, Daiga Murmane¹, Ieva Grinfelde¹, Liene Kornejeva¹, Zita Krumina¹, Olga Sterna¹, Ilze Radovica-Spalvina¹, Inta Vasiljeva¹, Linda Gailite¹, Janis Stavusis¹, Diana Livcane¹, Dita Kidere¹, Ieva Malniece¹, Inna Inashkina¹

Affiliation

¹ Medical Genetics Clinic (B.L., I. Micule, G.T., D.M., I.G., O.S., I. Malniece), Children's Clinical University Hospital; Latvian Biomedical Research and Study Centre (B.L., J. Stavusis, D.L., D.K., I.I.); Rare Disease Centre (V.K.), Riga East Clinical University Hospital; Neurology Department (S.S., J. Strautmanis, I.K.), Children's Clinical University Hospital; Riga Maternity Hospital (L.K.); Riga Stradins University (Z.K.); Genera Ltd (I.R.-S., I.V.); and Scientific Laboratory of Molecular Genetics (L.G.), Riga Stradins University, Riga, Latvia.

Abstract

Background and objectives: Genetic 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.

Methods: Patients with NMD from Latvia with molecular tests confirming their diagnosis in 2008-2020 were included in this retrospective study.

Results: Diagnosis 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.

Discussion: DNA 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.