From spastic paraplegia to infantile neurodegenerative disorder: Expanding the phenotypic spectrum associated with biallelic SPAST variants.

Purpose: Heterozygous pathogenic variants in SPAST are known to cause Hereditary Spastic Paraplegia 4 (SPG4), the most common form of HSP, characterized by progressive bilateral lower limbs spasticity with frequent sphincter disorders. However, there are very few descriptions in the literature of patients carrying biallelic variants in SPAST.

Methods: Targeted Sanger sequencing, panel sequencing and exome sequencing were used to identify the genetic causes in 9 patients from 6 unrelated families with symptoms of HSP or infantile neurodegenerative disorder.

Intensification of Diurnal Abnormal Movements During Sleep in Huntington's Disease.

Huntington's disease (HD) is a rare neurodegenerative disorder with a distinct phenotype, including involuntary movements, cognitive decline, and behavioral disturbances. Sleep disorder include insomnia, increased sleep onset latency, decrease in total sleep time with frequent nocturnal awakenings and excessive daytime sleepiness. Increased sleep motor activities and abnormal nocturnal agitation have been increasingly recognized as an important component affecting negatively the sleep quality.

CAG repeat mosaicism is gene specific in spinocerebellar ataxias.

Expanded CAG repeats in coding regions of different genes are the most common cause of dominantly inherited spinocerebellar ataxias (SCAs). These repeats are unstable through the germline, and larger repeats lead to earlier onset. We measured somatic expansion in blood samples collected from 30 SCA1, 50 SCA2, 74 SCA3, and 30 SCA7 individuals over a mean interval of 8.

Upstream open reading frame-introducing variants in patients with primary familial brain calcification.

More than 50% of patients with primary familial brain calcification (PFBC), a rare neurological disorder, remain genetically unexplained. While some causative genes are yet to be identified, variants in non-coding regions of known genes may represent a source of missed diagnoses. We hypothesized that 5'-Untranslated Region (UTR) variants introducing an AUG codon may initiate mRNA translation and result in a loss of function in some of the PFBC genes.