BPAN(beta-propeller protein-associated neurodegeneration)

A 13-year-old girl with infantile-onset self-resolving epilepsy and developmental delay had an unremarkable workup, including normal brain magnetic resonance imaging (MRI) and chromosomal microarray. During adolescence, she presented with features of early-onset parkinsonism: gait dyspraxia, freezing during walking, cogwheel rigidity in both upper extremities, and left arm dystonia. Repeat brain MRI showed iron deposition on the substantia nigra (SN) and basal ganglia, with hyperintense halo sign around a central linear hypointensity within the SN on the T1 imaging sequence...

Several patients with beta-propeller protein-associated neurodegeneration (BPAN)/static encephalopathy with neurodegeneration in adulthood have been reported to present Rett syndrome (RTT)-like features. This report presents an individual with BPAN showing clinical features of RTT. Psychomotor delay and epilepsy onset were noted at 1 year, and regression began at 4 years. Screening of the methyl-CpG binding protein 2 (MECP2) did not show variants. At 22 years, basal ganglia iron deposits were found on magnetic resonance imaging (MRI), and the WD-domain repeat 45 gene (WDR45) variant was identified...

BACKGROUND: Beta-propeller protein-associated neurodegeneration (BPAN) is a rare, X-linked dominant neurodegenerative disease mainly characterized by developmental delay, intellectual disability, epilepsy in childhood and dystonia, parkinsonism, dementia in adulthood. BPAN is caused by variants in WD repeat domain 45(WDR45), which is characterized by iron accumulation in the basal ganglia, however, it may be atypical in early brain MRI. METHODS: Whole exome sequencing was performed for five parents-offspring trios and phenotype-driven data analyses were conducted...

BACKGROUND: Neurodegeneration with brain iron accumulation constitutes a group of rare progressive movement disorders sharing intellectual disability and neuroimaging findings as common denominators. Beta-propeller protein-associated neurodegeneration (BPAN) represents approximately 7% of the cases, and its first signs are typically epilepsy and developmental delay. We aimed to describe in detail the phenotype of BPAN with a special focus on iron metabolism. MATERIAL AND METHODS: We present a cohort of paediatric patients with pathogenic variants of WD-Repeat Domain 45 gene (WDR45)...

OBJECTIVE: The early diagnosis of beta-propeller protein-associated neurodegeneration (BPAN) before distinct brain magnetic resonance imaging (MRI) findings of iron deposition occur remains challenging. This study examined whether children with BPAN have characteristic high-amplitude (>50 μV) fast activity (HAFA) on electroencephalography (EEG). METHODS: We conducted a retrospective analysis of EEG performed during childhood in five patients with BPAN. We also examined 143 EEGs from 59 patients with different etiologies, including epilepsy (n = 33), acute encephalopathy (n = 6), neurodevelopmental disorders (n = 5), non-epileptic events (n = 4), and others (n = 11)...

BACKGROUND AND PURPOSE: Beta-propeller protein-associated neurodegeneration (BPAN) is one subtype of neurodegeneration with brain iron accumulation. It is difficult to diagnose BPAN due to the non-specificity of their clinical findings and neuroimaging in early childhood. We experienced four pediatric patients with serial brain MRI and evaluated the alteration of the findings through their course. METHODS: We retrospectively reviewed the clinical findings and 21 MRI findings of the four patients with genetically confirmed pediatric BPAN...

Beta-propeller protein-associated neurodegeneration (BPAN) is categorized in Neurodegeneration with brain iron accumulation. The clinical feature of BPAN is global developmental delay in early childhood, followed rapid progression of cognitive disfunction and parkinsonism in adulthood. This case was pointed out intellectual disability at the age of 9, followed left dominant progressive parkinsonism from the age of 31. Brain MRI showed the T1 -weighted signal hyperintensity of the substantia nigra with a central band of hypointensity and the T2 star weighted image hypointensity of substantia nigra and globus pallidus presenting dominant at right side...

This report discusses a 13-year-old girl diagnosed with beta-propeller protein-associated neurodegeneration (BPAN). BPAN is an X-linked neurodegeneration disorder associated with a mutation in the WDR45 gene. It typically presents in childhood with encephalopathy, developmental delay, and seizures. Following an initial static phase, these symptoms then progress to dementia, dystonia, and parkinsonism in early adulthood. Our child initially presented with epileptic spasms, global developmental delay, speech delay, hypotonia, spasticity, scoliosis, and gait disturbance...

Beta-propeller protein-associated neurodegeneration (BPAN) is caused by mutations in the autophagy gene WDR45/WIPI4 . In human, BPAN is associated with static encephalopathy in childhood and neurodegeneration in adulthood (SENDA). It has been proposed that WDR45 mutations cause neurodegeneration due to defective autophagy. Whether these mutations cause a global attenuation or a defect in a subset of autophagy functions is unknown. Based on a recent study showing that wdr45 knockout mice exhibit defective autophagy associated with an increased ER stress, we propose that ER-mediated autophagy, a selective activation of autophagy, is defective in mouse and cellular models of BPAN...

INTRODUCTION: Beta-propeller protein-associated neurodegeneration (BPAN) is a very rare, X-linked dominant (XLD) inherited member of the neurodegeneration with brain iron accumulation (NBIA) disease family. CASE REPORT: We present a female case of BPAN with infantile spasms in the first year, Rett-like symptomatology, focal epilepsy, and loss of motor skills in childhood. Menarche occurred at the age of 9, after precocious pubarche and puberty.Dystonia-parkinsonism as extrapyramidal sign at the age of 10 years resulted in radiological and genetic work-up...

BACKGROUND: Beta-propeller protein-associated neurodegeneration (BPAN, OMIM 300894) is an X-linked neurodegenerative disorder caused by mutations in WDR45. WDR45 is required for autophagy, defect in WDR45 impaired autophagy which contributes for the pathogenesis of BPAN. Previously, we reported a novel de novo mutation (c.1040_1041del, p.Glu347GlyfsTer7) in WDR45 (NM_007075) in a 3-year-old Chinese girl with BPAN. METHODS: The protein structure was constructed using SWISS-MODEL and the isoelectric point (pI) was predicted by the online pI/Mw tool at ExPASy...

Beta-propeller protein-associated neurodegeneration (BPAN) is a subtype of neurodegeneration with brain iron accumulation (NBIA) that presents with childhood developmental delay (especially speech delay), occasionally associated with epileptic encephalopathy, autism, or Rett-like syndrome. The majority of children described to date have been severely affected, with little to no expressive speech function, severe developmental delay, and cognitive impairment. Herein, five additional patients with BPAN identified in the same center in Canada are described, four with the typical severe phenotype and one with a milder phenotype...

Macroautophagy/autophagy functions as a quality control mechanism by degrading misfolded proteins and damaged organelles and plays an essential role in maintaining neural homeostasis. The phosphoinositide phosphatidylinositol-3-phosphate (PtdIns3P) effector Atg18 is essential for autophagosome formation in yeast. Mammalian cells contain four Atg18 homologs, belonging to two subclasses, WIPI1 (WD repeat domain, phosphoinositide interacting 1), WIPI2 and WDR45B/WIPI3 (WD repeat domain 45B), WDR45/WIPI4. The role of Wdr45b in autophagy and in neural homeostasis, however, remains unknown...

Beta-propeller protein-associated neurodegeneration (BPAN) is an X-linked rare dominant disorder of autophagy. The role of WDR45 has been implicated in BPAN almost exclusively in females possibly due to male lethality. Characterization of distinctive clinical manifestations and potentially the complex genetic determinants in rare male patients remain crucial for deciphering BPAN and other X-linked dominant diseases. We performed whole exome sequencing (WES) followed by segregation analysis and identified a novel nonsense and mosaic variant in WDR45, namely NM_007075...

BACKGROUND Ischemic fasciitis is a rare condition that occurs in debilitated and immobilized individuals, usually overlying bony protuberances. Because the histology shows a pseudosarcomatous proliferation of atypical fibroblasts, and because the lesion can increase in size, ischemic fasciitis can mimic sarcoma. Beta-propeller protein-associated neurodegeneration (BPAN) arises in infancy and is due to mutations in the WDR45 gene on the X chromosome. BPAN results in progressive symptoms of dystonia, Parkinsonism, and dementia once the individual reaches adolescence or early adulthood, and is usually fatal before old age...

WDR45 gene-associated neurodegeneration with brain iron accumulation (NBIA), referred to as beta-propeller protein-associated neurodegeneration (BPAN), is a rare disorder that presents with a very nonspecific clinical phenotype in children constituting global developmental delay. This case report illustrates the power of a combination of trio exome sequencing, in silico splicing analysis, and mRNA analysis to provide sufficient evidence for pathogenicity of a relatively intronic variant in WDR45, and in so doing, find a genetic diagnosis for a 6-year-old patient with developmental delay and seizures, a diagnosis which may otherwise have only been found once the characteristic MRI patterns of the disease became more obvious in young adulthood...

Beta-propeller protein-associated neurodegeneration (BPAN) is a rare disorder, which is increasingly recognized thanks to next-generation sequencing. Due to a highly variable phenotype, patients may present to pediatrics, neurology, psychiatry, or internal medicine. It is therefore essential that physicians of different specialties are familiar with this severe and debilitating condition.

Heterozygous de novo variants in the autophagy gene, WDR45, are found in beta-propeller protein-associated neurodegeneration (BPAN). BPAN is characterized by adolescent onset dementia and dystonia; 66% patients have seizures. We asked whether WDR45 was associated with developmental and epileptic encephalopathy (DEE). We performed next generation sequencing of WDR45 in 655 patients with developmental and epileptic encephalopathies. We identified 3/655 patients with DEE plus 4 additional patients with de novo WDR45 pathogenic variants (6 truncations, 1 missense); all were female...

BACKGROUND: Static encephalopathy of childhood with neurodegeneration in adulthood is a phenotypically distinctive, X-linked dominant subtype of neurodegeneration with brain iron accumulation (NBIA). WDR45 mutations were recently identified as causal. WDR45 encodes a beta-propeller scaffold protein with a putative role in autophagy, and the disease has been renamed beta-propeller protein-associated neurodegeneration (BPAN). CASE REPORT: Here we describe a female patient suffering from a classical BPAN phenotype due to a novel heterozygous deletion of WDR45 ...

Mutations in WDR45 are responsible for beta-propeller protein-associated neurodegeneration (BPAN), which is an X-linked form of neurodegeneration with brain iron accumulation. BPAN mainly affects females and is characterized by seizures and developmental delay or intellectual disability until adolescence or early adulthood, followed by severe dystonia, parkinsonism, and progressive dementia. However, rare male patients have recently been reported with hemizygous germline mutations in WDR45 and severe clinical manifestations, such as epileptic encephalopathies...