Frontiers in Neurology | Neurogenetics section | New and Recent Articles

BackgroundNeuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder caused by NOTCH2NLC GGC repeat expansions. Renal involvement in NIID is not well understood.MethodsWe conducted a cross-sectional study of 96 genetically confirmed NIID patients. Renal function was comprehensively assessed using the estimated glomerular filtration rate (eGFR) derived from the 2021 Chroni…

IntroductionWilson disease is an autosomal recessive monogenic disorder caused by mutations in the copper-transporting P-type ATPase beta gene (ATP7B) located on human chromosome 13. This gene encodes copper-transporting P-type ATPase. This article reports a case of Wilson disease with a novel ATP7B deletion variant.Case reportWe report a case of Wilson disease in a Chinese female patient. Cirrho…

BackgroundGenetic testing in amyotrophic lateral sclerosis (ALS) is increasingly recommended for all patients, but real-world implementation in middle-income countries remains heterogeneous. Brazilian motor neuron disease genetics has largely been characterized through protocol-based cohorts focused on the founder VAPB p.Pro56Ser variant (amyotrophic lateral sclerosis type 8, ALS8). The broader g…

BackgroundAmyotrophic lateral sclerosis (ALS) associated with mutations in the superoxide dismutase 1 (SOD1) gene is recognized for phenotypic variability, yet cerebellar ataxia as a presenting feature has been reported only in isolated cases.MethodsWe describe four unrelated patients: three men and one woman, aged 35 to 49 years at symptom onset, who carried the SOD1 D91A (p.Asp91Ala) mutation. …

Amyotrophic lateral sclerosis (ALS) is a complex and progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motor neurons. Although most ALS cases occur sporadically, without a known family history of the disease, genetic factors play a major role in its pathogenesis through monogenic, oligogenic, or polygenic mechanisms. It is estimated that 10–15% of AL…

IntroductionParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized pathologically by the accumulation and propagation of α-synuclein (α-syn). Although α-syn aggregation is considered central to PD pathogenesis, increasing evidence suggests that α-syn abundance may be as important as its conformational state. Genetic studies have demonstrated an SNCA dosage effect, with…

BackgroundRett syndrome (RTT) is a rare, progressive MECP2-related neurodevelopmental disorder with substantial lifelong morbidity that persists into adulthood. Although survival has improved, adults often experience evolving multisystem complications and fragmented transition care. Trofinetide (TROF) is approved for ages ≥2 years old, yet data on adults with RTT in the real-world setting remains…

Mitochondrial dysfunction is a central feature of neurodegenerative diseases, yet the molecular mechanisms governing mitochondrial protein synthesis remain insufficiently understood. Mitochondrial ribosomal proteins (MRPs), essential for the translation of mitochondrial-encoded components of the oxidative phosphorylation system, are emerging as critical regulators of neuronal homeostasis and surv…

BackgroundInter-individual variability in efficacy and tolerability remains a major challenge in psychiatric prescribing. Pharmacogenomics (PGx) has been proposed as a practical tool to reduce avoidable drug-gene mismatches, particularly for antidepressants and selected antipsychotics metabolized by CYP2D6 and CYP2C19. However, the clinical value of PGx in psychiatry is uneven across drug classes…

BackgroundChromatin-modifying systems regulate transcriptional programs essential for human neurodevelopment through dynamic modification of histones, DNA, and higher-order chromatin architecture. Pathogenic variants affecting these systems give rise to chromatinopathies, a heterogeneous group of disorders characterised by consistent neurological features, including intellectual disability, devel…

IntroductionWe leveraged consanguinity and population endogamy in a large four generation Turkish family with ET. Examination of clinical features and genetic analysis identified a homozygous PRPF40B missense variant, in a large region of homozygosity, segregating with ET in the family.MethodsThe ET family is of Turkish origin. The proband and relatives were evaluated at Ankara University Medical…

Ceramide transporter syndrome (CerTra syndrome) is a rare neurodevelopmental disorder caused by pathogenic variants in CERT1 gene encoding ceramide transporter (CERT). These variants disrupt ceramide transport and sphingolipid homeostasis, leading to a clinical phenotype that includes developmental delay, movement abnormalities, and structural brain anomalies. Despite growing recognition of this …

Leigh syndrome (LS) is a prevalent mitochondrial encephalomyopathy in childhood, triggered by mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). The protein encoded by the SURF1 gene localizes to the inner mitochondrial membrane and is involved in the biosynthesis of the cytochrome c oxidase (COX) complex. We enrolled 5 children harboring SURF1 gene variants whose clinical manifestatio…

BackgroundAbnormal cortical neuron development is closely associated with various neurological disorders. Deletion of the Alg13 gene has been identified as strongly associated with epilepsy susceptibility and seizure severity in mice. Similar deletions have also been observed in patients with epilepsy, indicating that Alg13 may play a critical role in cortical interneuron development.MethodsImmun…

Leigh syndrome (LS) is the most common pediatric mitochondrial disorder, typically presenting in infancy with developmental regression, neurological dysfunction, and characteristic brain MRI lesions. It is linked to over 110 genes affecting cellular energy production, making it highly genetically heterogeneous, with complex I deficiency being the most frequent cause. Biallelic mutations in NDUFAF…

IntroductionCerebral Palsy (CP) is characterized by permanent, non-degenerative motor function deficits with increasing evidence of genetic contributions. Although prenatal and perinatal risk factors are well recognized, the underlying etiopathology remains incompletely understood. This study aimed to improve diagnostic accuracy and elucidate the genetic architecture of CP and CP-like phenotypes …

SYNGAP1-related neurodevelopmental disorder (SRD) is a monogenic inherited brain disorder caused by heterozygous loss-of-function mutations in the SYNGAP1 gene. The clinical presentation is complex, with core features including global developmental delay/intellectual disability, epilepsy, autism spectrum disorder, and various behavioral abnormalities. The SynGAP protein, encoded by the SYNGAP1 ge…