The gene product (protein PTCD3 or MRPS39) forms the entry channel of the mitochondrial small ribosomal subunit and binds to single-stranded mRNA. Here, we expand on the clinical manifestations of pathogenic variants by describing an early-onset patient with Leigh-like syndrome and two patients with milder form of disease, with combined oxidative phosphorylation deficiency. A 34-year-old male and his 33-year-old sister both have horizontal nystagmus, pronounced rough tremor, truncal ataxia, dysmetria, spasticity and hyperreflexia.
View Article and Find Full Text PDF: Danon disease is a multisystemic disorder associated with variants in the gene, mainly affecting the cardiac muscle. Here, we report a multigenerational family from Latvia with two male patients, hemizygous for a novel splice-affecting variant c.928+3A>G.
View Article and Find Full Text PDFObjective: Netherton syndrome (NS) (OMIM:256500) is a very rare autosomal recessive multisystem disorder mostly affecting ectodermal derivatives (skin and hair) and immune system. It is caused by biallelic loss-of-function variants in the SPINK5 gene, encoding the protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI).
Material, Methods And Results: Here, we describe NS clinical and genetic features of homogenous patient group: 9 individuals from 7 families with similar ethnic background and who have the same SPINK5 variant (NM_006846.
HINT1 is an ubiquitous homodimeric purine phosphoramidase belonging to the histidine-triad superfamily. In neurons, HINT1 stabilizes the interaction of different receptors and regulates the effects of their signaling disturbances. Changes in gene are associated with autosomal recessive axonal neuropathy with neuromyotonia.
View Article and Find Full Text PDFBackground 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.
View Article and Find Full Text PDFThe investigated intronic CAPN3 variant NM_000070.3:c.1746-20C>G occurs in the Central and Eastern Europe with a frequency of >1% and there are conflicting interpretations on its pathogenicity.
View Article and Find Full Text PDFInt J Neonatal Screen
February 2022
New disease-modifying treatments have recently been approved for 5q spinal muscular atrophy (SMA) and early treatment has been associated with a better clinical outcome. Accordingly, new-born screening (NBS) for SMA should be implemented to ensure early diagnosis of affected individuals. The aim of this study was to determine the feasibility and usefulness of NBS for SMA in Latvia.
View Article and Find Full Text PDFThere are recent reports of associations of variants in the gene with a hereditary neurological disease that presents with a wide spectrum of clinical severity, ranging from severe neonatal encephalopathy with no psychomotor development to adolescent-onset uncomplicated spastic paraplegia. Here, we report two probands from unrelated families presenting with severe and intermediate variations of the clinical course. A homozygous variant in the gene was detected in each proband; however, there was no known parental consanguinity.
View Article and Find Full Text PDFBACKGROUND Parental chromosomal structural abnormalities can lead to diverse chromosomal imbalances at meiotic segregation during gametogenesis and subsequent early pregnancy loss or birth of a child with a chromosomal abnormality. The incidence of unbalanced translocations is 1 per 1000 newborns versus 3 per 1000 newborns for balanced rearrangements. Here, we present the case of a mother with an unbalanced chromosomal translocation and her offspring.
View Article and Find Full Text PDFKohlschütter-Tönz syndrome (KTS) is a rare, autosomal recessive syndrome characterized by a triad of epilepsy, amelogenesis imperfecta and severe global developmental delay. It was first described in a Swiss family in 1974 by Alfried Kohlschütter and Otmar Tönz. It is caused by pathogenic variants in the ROGDI gene.
View Article and Find Full Text PDFLeigh 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.
View Article and Find Full Text PDFBackground And Purpose: Charcot-Marie-Tooth (CMT) disease is a chronic, slowly progressing disorder. The lack of specific disease progression biomarkers limits the execution of clinical trials. However, neurofilament light chain (NfL) has been suggested as a potential biomarker for peripheral nervous system disorders.
View Article and Find Full Text PDFRecently the scientific community has started to view Bethlem myopathy 1 and Ullrich congenital muscular dystrophy as two extremes of a collagen VI-related myopathy spectrum rather than two separate entities, as both are caused by mutations in one of the collagen VI genes. Here we report three individuals in two families who are homozygous for a COL6A3 mutation (c.7447A> G; p.
View Article and Find Full Text PDFBackground: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by allelic variants in gene. More than 500 distinct variants have been reported, the most common WD causing allelic variant in the patients from Central, Eastern, and Northern Europe is H1069Q.
Methods: All Latvian patients with clinically confirmed WD were screened for the most common mutation p.
Background: Limb-girdle muscular dystrophies are characterized by predominant involvement of the shoulder and pelvic girdle and trunk muscle groups. Currently, there are 31 genes implicated in the different forms of limb-girdle muscular dystrophies, which exhibit similar phenotypes and clinical overlap; therefore, advanced molecular techniques are required to achieve differential diagnosis.
Methods: We investigated 26 patients from Latvia and 34 patients from Lithuania with clinical symptoms of limb-girdle muscular dystrophies, along with 565 healthy unrelated controls from general and ethnic populations using our developed test kit based on the Illumina VeraCode GoldenGate genotyping platform, Ion AmpliSeq Inherited Disease Panel and direct sequencing of mutations in calpain 3 (CAPN3), anoctamin 5 (ANO5) and fukutin related protein (FKRP) genes.
Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder with distinct facies, growth failure, intellectual disability, distal limb anomalies, gastrointestinal and neurological disease. Mutations in NIPBL, encoding a cohesin regulatory protein, account for >80% of cases with typical facies. Mutations in the core cohesin complex proteins, encoded by the SMC1A, SMC3 and RAD21 genes, together account for ∼5% of subjects, often with atypical CdLS features.
View Article and Find Full Text PDFCase Rep Neurol Med
September 2013
Limb-girdle muscular dystrophies (LGMDs) is a heterogeneous group of muscular dystrophies that mostly affect the pelvic and shoulder girdle muscle groups. We report here a case of neuromuscular disease associated with Dupuytren's contracture, which has never been described before as cosegregating with an autosomal dominant type of inheritance. Dupuytren's contracture is a common disease, especially in Northern Europe.
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