P318: Ironing out the BPAN phenotypic spectrum: A report of three new BPAN cases and review of the literature
Notice bibliographique
Résumé
Neurodegeneration with brain iron accumulation (NBIA) refers to a spectrum of disorders, which as the name suggests, involve abnormal iron accumulation within the brain that leads to progressive nervous system degeneration. NBIA type 5, which is more commonly referred to as Beta-propeller protein-associated neurodegeneration (BPAN), is one example of a disorder within this group. BPAN is an X-linked condition and is typically caused by loss of function mutations in the WDR45 gene. Classically, BPAN has been characterized by global developmental delay and seizures in childhood, followed by neurodegeneration in adulthood. Neurological symptoms can progress to include parkinsonism, dystonia, and dementia. Since it was first reported in 2012, the phenotypic spectrum observed with BPAN has greatly expanded. The most recent review of disease associated with WDR45 was in 2020, at which time there were 123 individuals identified with WDR45-related disease. New case reports of patients with BPAN continue to be published, and additional patients continue to be diagnosed. We have identified three new cases of BPAN as well as provided updated clinical information on a previously reported case. All four patients are followed at a single center in Saskatchewan, Canada. Identification of WDR45 variants was accomplished through multi-gene testing panels or whole exome sequencing. Of the three unpublished cases, two of the patients were found to have de novo pathogenic frameshift variants (NM_007075.3: c.964del, p.Lys319Argfs*11 and NM_007075.3: c.561_564dup, p.Ile189Hisfs*8). The third patient was found to have a missense variant of uncertain significance (NM_007075.3: c.359T>C, p.Ile62Val) but with clinical signs and symptoms supporting a BPAN diagnosis. The patients range from 10 to 17 years of age. All the patients in the cohort are followed for seizures, however, only the oldest patient has started to exhibit some features of parkinsonism. One of the patients presents with iron deposition in the lungs, which has yet to be reported with WDR45-related disease in the literature. Improved awareness of the phenotypic variability of BPAN, the uptake of more comprehensive diagnostic modalities like whole exome sequencing, as well as advances in neuroimaging have greatly improved clinicians’ abilities to diagnose the disease. We aimed to provide a case series including three newly identified patients as well as provide an update on BPAN literature. This work further elucidates the phenotypic variability seen with WDR45 variants. In turn, it contributes to the body of literature regarding WDR45 related disease, which ultimately serves to facilitate earlier disease diagnosis for affected patients.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».