Novel SPR mutation in first Chinese patient with sepiapterin reductase deficiency: urinary biomarker validation in oldest treated case.

Background: Sepiapterin reductase deficiency (SRD) is a rare disorder characterized by motor and cognitive symptoms, where early diagnosis and treatment can significantly improve patient outcomes.

Methods: We performed genetic analysis, functional studies including Western blot and immunocytochemistry, and urinary sepiapterin measurements in a Chinese patient presenting with levodopa-responsive dystonia and parkinsonism.

Results: We identified a novel homozygous mutation (c.

Novel Phenotypes and Deep Intronic Variant Expand TH-Associated Dopa-Responsive Dystonia Spectrum.

Approximately 20% of dopa-responsive dystonia (DRD) cases remain genetically unresolved. Using whole-genome sequencing, we identified two TH variants in a young DRD patient, including a novel deep intronic variant. Minigene assays confirmed that this variant causes aberrant splicing.

Long-read sequencing revealed complex biallelic pentanucleotide repeat expansions in RFC1-related Parkinson's disease.

Biallelic intronic pentanucleotide repeat expansions, mainly (AAGGG)exp and/or (ACAGG)exp in RFC1, are detected in cerebellar ataxia, neuropathy and vestibular areflexia syndrome, late-onset ataxia, and in a wide disease spectrum including Charcot-Marie-Tooth disease, multiple system atrophy, and Parkinson's disease (PD). However, the genotype-phenotype correlation and underlying mechanism are mostly unknown. We screened RFC1-repeat expansions in 1445 patients with parkinsonism.

Unveiling distinct clinical manifestations of primary familial brain calcifications in Asian and European patients: A study based on 10-year individual-level data.

Background: Primary Familial Brain Calcification (PFBC) can manifest clinically with a complex and heterogeneous array of symptoms, including parkinsonism, dysarthria, and cognitive impairment. However, the distinct presentations of PFBC in Asian and European populations remain unclear.

Methods: We conducted a systematic search of PubMed for studies involving genetically confirmed PFBC patients.

A Homozygous Variant in NAA60 Is Associated with Primary Familial Brain Calcification.

Background: Primary familial brain calcification (PFBC) is a monogenic disorder characterized by bilateral calcifications in the brain. The genetic basis remains unknown in over half of the PFBC patients, indicating the existence of additional novel causative genes. NAA60 was a recently reported novel causative gene for PFBC.

Neurofilament light chain as a mediator between LRRK2 mutation and dementia in Parkinson's disease.

Elevated neurofilament light chain (NfL) levels have been associated with dementia in idiopathic Parkinson's disease (iPD). To examine the baseline and longitudinal changes in NfL levels in GBA-PD, SNCA-PD, and LRRK2-PD and further investigate the association between these genetic mutations, NfL, and dementia in PD. We analyzed data from the Parkinson's Progression Markers Initiative (PPMI), including 184 healthy controls (HC) and 617 PD categorized as iPD (n = 381), LRRK2-PD (n = 142), GBA-PD (n = 76) and SNCA-PD (n = 18).