BMC medical genomics · 2021
A new family with spastic paraplegia type 51 and novel mutations in AP4E1.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Winkler Izabela, Miotła Paweł, Lejman Monika, Pietrzyk Aleksandra, Kacprzak Magdalena, Kubiak Marcin, Sobczyńska-Tomaszewska Agnieszka, Skrzypczak Maciej, Jaszczuk Ilona
Аннотация
BACKGROUND: Autosomal recessive mutations in the AP-4 (adaptor protein complex 4) complex subunit ϵ - 1 (AP-4E1) gene on chromosome 15q21.2 are known to cause spastic paraplegia 51 (SPG51). The exact phenotype of SPG51 remains poorly characterized, because only a few families have been reported as carriers of the mutation. In addition, a previous study identified an autosomal dominant mutation in the AP4E1 gene as being associated with persistent stuttering. The aim of the current study was to characterize the phenotype of a paediatric patient with an identified novel AP4E1 mutation presenting with significant psychomotor retardation, intellectual disability and paraplegia.
METHODS: Magnetic resonance imaging was used to identify hypoplasia of the corpus callosum. The DNA sample was tested using multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH). In addition, next-generation sequencing (NGS) was performed using the patient's DNA, and Sanger sequencing was performed using that of his family members.
RESULTS: The phenotype was identified to be associated with a novel pathogenic variant c.942_943 + 3delinsCC in the AP4E1 gene. The patient manifested severely delayed psychomotor development, impaired global physical development and general illness. Movement disorders were evident during the neonatal period.
CONCLUSIONS: The present study identifies a previously unknown disease-inducing AP4E1 gene mutation.
METHODS: Magnetic resonance imaging was used to identify hypoplasia of the corpus callosum. The DNA sample was tested using multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH). In addition, next-generation sequencing (NGS) was performed using the patient's DNA, and Sanger sequencing was performed using that of his family members.
RESULTS: The phenotype was identified to be associated with a novel pathogenic variant c.942_943 + 3delinsCC in the AP4E1 gene. The patient manifested severely delayed psychomotor development, impaired global physical development and general illness. Movement disorders were evident during the neonatal period.
CONCLUSIONS: The present study identifies a previously unknown disease-inducing AP4E1 gene mutation.