دورية أكاديمية
Bi-allelic variants in CHKA cause a neurodevelopmental disorder with epilepsy and microcephaly
| العنوان: | Bi-allelic variants in CHKA cause a neurodevelopmental disorder with epilepsy and microcephaly |
|---|---|
| المؤلفون: | Klöckner, Chiara, Murray, J Pedro Fernandez, Tavasoli, Mahtab, Sticht, Heinrich, Stoltenburg-Didinger, Gisela, Scholle, Leila Motlagh, Bakhtiari, Somayeh, Kruer, Michael C, Darvish, Hossein, Firouzabadi, Saghar Ghasemi, Pagnozzi, Alex, Shukla, Anju, Girisha, Katta Mohan, Narayanan, Dhanya Lakshmi, Kaur, Parneet, Maroofian, Reza, Zaki, Maha S, Noureldeen, Mahmoud M, Merkenschlager, Andreas, Gburek-Augustat, Janina, Cali, Elisa, Banu, Selina, Nahar, Kamrun, Efthymiou, Stephanie, Houlden, Henry, Jamra, Rami Abou, Williams, Jason, McMaster, Christopher R, Platzer, Konrad |
| المصدر: | Brain , 145 (6) pp. 1916-1923. (2022) |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2022 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | Kennedy pathway, choline kinase alpha, epilepsy, exome sequencing, neurodevelopmental disorder |
| الوصف: | The Kennedy pathways catalyze the de novo synthesis of phosphatidylcholine and phosphatidylethanolamine, the most abundant components of eukaryotic cell membranes. In recent years, these pathways have moved into clinical focus since four out of ten genes involved have been associated with a range of autosomal recessive rare diseases such as a neurodevelopmental disorder with muscular dystrophy (CHKB), bone abnormalities and cone-rod dystrophy (PCYT1A), and spastic paraplegia (PCYT2, SELENOI). We identified six individuals from five families with bi-allelic variants in CHKA presenting with severe global developmental delay, epilepsy, movement disorders, and microcephaly. Using structural molecular modeling and functional testing of the variants in a in a cell-based S. cerevisiae model, we determined that these variants reduce the enzymatic activity of CHKA and confer a significant impairment of the first enzymatic step of the Kennedy pathway. In summary, we present CHKA as a novel autosomal recessive gene for a neurodevelopmental disorder with epilepsy and microcephaly. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/10144526/1/awac074.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10144526Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/10144526/1/awac074.pdfTest https://discovery.ucl.ac.uk/id/eprint/10144526Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.32FD50C5 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |