Two Cases of Leigh Syndrome in One Family : Diagnostic Challenges and Clinical Management Experience in Latvia

Publisher Copyright: © 2021 Arta Katkevica et al.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.publishersversionPeer reviewe

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

Funding Information: The Article Processing Charge was funded by the authors. Publisher Copyright: © American Academy of Neurology.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.publishersversionPeer reviewe

Case of Inherited Partial AZFa Deletion without Impact on Male Fertility

Male factor infertility accounts for 40–50% of all infertility cases. Deletions of one or more AZF region parts in chromosome Y are one of the most common genetic causes of male infertility. Usually full or partial AZF deletions, including genes involved in spermatogenesis, are associated with spermatogenic failure. Here we report a case of a Caucasian man with partial AZFa region deletion from a couple with secondary infertility. Partial AZFa deletion, involving part of USP9Y gene appears to be benign, as we proved transmission from father to son. According to our results, it is recommended to revise guidelines on markers selected for testing of AZFa region deletion, to be more selective against DDX3Y gene and exclude probably benign microdeletions involving only USP9Y gene.publishersversionPeer reviewe

The outcomes after transfers of embryos with chromosomal mosaicism : a single reproductive medicine center experience at iVF Riga clinic

Publisher Copyright: © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the UR MED GRUPP (LLC). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Aim: The aim of this study is to summarize the outcomes of transfers of mosaic embryos, which were classified according to guidelines and in strong collaboration of reproductologists, clinical geneticists and patients approved as suitable for transfer. Material and Methods: Retrospective data were collected from 70 patients from a private IVF center to whom embryos with mosaic changes in chromosomal material were transferred from 2015 to 2019. Results and Conclusion: Implantation outcomes and continuing pregnancies showed slight differences, when compared to fully normal embryos. Artifacts have to be differentiated from undeniable aberrations, and correct interpretation of results must be done with following patient counselling and prenatal testing if necessary.publishersversionPeer reviewe

Prenatal phenotyping: A community effort to enhance the Human Phenotype Ontology.

Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and translational research in human genetics. To better support prenatal usage, the HPO consortium conducted a series of workshops with a group of domain experts in a variety of medical specialties, diagnostic techniques, as well as diseases and phenotypes related to prenatal medicine, including perinatal pathology, musculoskeletal anomalies, neurology, medical genetics, hydrops fetalis, craniofacial malformations, cardiology, neonatal-perinatal medicine, fetal medicine, placental pathology, prenatal imaging, and bioinformatics. We expanded the representation of prenatal phenotypes in HPO by adding 95 new phenotype terms under the Abnormality of prenatal development or birth (HP:0001197) grouping term, and revised definitions, synonyms, and disease annotations for most of the 152 terms that existed before the beginning of this effort. The expansion of prenatal phenotypes in HPO will support phenotype-driven prenatal exome and genome sequencing for precision genetic diagnostics of rare diseases to support prenatal care

Prenatal phenotyping: A community effort to enhance the Human Phenotype Ontology

Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and translational research in human genetics. To better support prenatal usage, the HPO consortium conducted a series of workshops with a group of domain experts in a variety of medical specialties, diagnostic techniques, as well as diseases and phenotypes related to prenatal medicine, including perinatal pathology, musculoskeletal anomalies, neurology, medical genetics, hydrops fetalis, craniofacial malformations, cardiology, neonatal-perinatal medicine, fetal medicine, placental pathology, prenatal imaging, and bioinformatics. We expanded the representation of prenatal phenotypes in HPO by adding 95 new phenotype terms under the Abnormality of prenatal development or birth (HP:0001197) grouping term, and revised definitions, synonyms, and disease annotations for most of the 152 terms that existed before the beginning of this effort. The expansion of prenatal phenotypes in HPO will support phenotype-driven prenatal exome and genome sequencing for precision genetic diagnostics of rare diseases to support prenatal care

A novel EDA variant causing X-linked hypohidrotic ectodermal dysplasia : Case report

Publisher Copyright: © 2021 The AuthorsHereditary ectodermal dysplasias are a complex group of inherited disorders characterised by abnormalities in two or more ectodermal derivatives (skin, nails, sweat glands, etc.). There are two main types of these disorders – hidrotic and hypohidrotic/anhidrotic ectodermal dysplasias. Hypohidrotic ectodermal dysplasia (HED) or Christ-Siemens-Touraine syndrome (OMIM: 305100) occurs in 1 out of 5000–10,000 births [19] and has an X-linked recessive inheritance pattern (X-linked hypohydrotic ectodermal dysplasia – XLHED) [2]. The main cause of XLHED is a broad range of pathogenic variants in the EDA gene (HGNC:3157, Xq12-13) which encodes the transmembrane protein ectodysplasin-A [4]. We report here the case of a patient with a novel inherited allelic variant in the EDA gene – NM_001399.5:c.337C>T (p.Gln113*) – in the heterozygous state. Targeted family member screening was conducted and other carriers of this EDA gene pathogenic variant were identified and phenotypically characterised. The patient subsequently underwent in vitro fertilisation with preimplantation genetic testing for monogenic diseases (PGT-M).publishersversionPeer reviewe