AP4B1-associated hereditary spastic paraplegia: expansion of phenotypic spectrum related to homozygous p.Thr387fs variant.
Krzysztof SzczalubaHanna MierzewskaSmigiel RobertJoanna KosińskaAgnieszka KoppoluAnna BiernackaPiotr StawińskiAgnieszka PollakMalgorzata RydzaniczPloski RafalPublished in: Journal of applied genetics (2020)
Biallelic mutations in the AP4B1 gene, encoding adaptor-related protein complex 4 beta-1 subunit, have been recognized as an important cause of a group of conditions leading to adaptor-related protein complex 4 (AP4)-associated hereditary spastic paraplegia (SPG47). We describe a homozygous, known variant c.1160_1161delCA (p.Thr387fs) that was found in the largest ever group of patients coming from four families. The patients exhibited early hypotonia progressing to spastic paraplegia, microcephaly, epilepsy, and central nervous system (CNS) defects and global developmental delay that are consistent with the nature of SPG47. Our findings expand phenotypic spectrum of SPG47 to include polymorphic seizures, mild/moderate intellectual disability, and intracerebral cysts as well as point to founder mutation in AP4 deficiency disorders in apparently non-consanguineous Polish families without shared ancestry.
Keyphrases
- intellectual disability
- end stage renal disease
- transcription factor
- ejection fraction
- newly diagnosed
- chronic kidney disease
- autism spectrum disorder
- prognostic factors
- peritoneal dialysis
- cerebral palsy
- zika virus
- gene expression
- dna methylation
- blood brain barrier
- high intensity
- genome wide
- copy number
- genome wide analysis