دورية أكاديمية
Genotype-phenotype correlations of STXBP1 pathogenic variants and the treatment choices for STXBP1-related disorders in China
| العنوان: | Genotype-phenotype correlations of STXBP1 pathogenic variants and the treatment choices for STXBP1-related disorders in China |
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| المؤلفون: | Miriam Kessi, Baiyu Chen, Li-Dan Shan, Ying Wang, Lifen Yang, Fei Yin, Fang He, Jing Peng, Guoli Wang |
| المصدر: | BMC Medical Genomics, Vol 16, Iss 1, Pp 1-10 (2023) |
| بيانات النشر: | BMC, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Internal medicine LCC:Genetics |
| مصطلحات موضوعية: | STXBP1-related disorders, Genotype-phenotype correlation, Intellectual disability, Global developmental delay, Epilepsy, Treatments, Internal medicine, RC31-1245, Genetics, QH426-470 |
| الوصف: | Abstract Background We aimed to analyze the genotype-phenotype correlations of STXBP1 pathogenic variants, prognostic factors and the treatment choices in a case-series of STXBP1-related disorders from China. Methods The clinical data and genetic results of the children diagnosed with STXBP1-related disorders at Xiangya hospital from 2011 to 2019 were collected retrospectively, and analyzed. We divided our patients into groups for comparison purposes: patients with missense variants and nonsense variants, patients who are seizure-free and not seizure-free, patients with mild to moderate intellectual disability (ID) and severe to profound global developmental delay (GDD). Results Nineteen patients were enrolled: 17 (89.5%) unrelated and 2 (10.5%) familial. Twelve (63.2%) were females. Developmental epileptic encephalopathy (DEE) was observed in 18 (94.7%) patients and ID alone in 1 (5.3%) individual. Thirteen patients (68.4%) had profound ID/GDD, 4 (23.53%) severe, 1 (5.9%) moderate and 1 (5.9%) mild. Three patients (15.8%) with profound ID died. A total of 19 variants were detected: pathogenic (n = 15) and likely pathogenic (n = 4). Seven were novel variants: c.664-1G>-, M486R, H245N, H498Pfs*44, L41R, L410del, and D90H. Of the 8 previous reported variants, 2 were recurrent: R406C and R292C. Anti-seizure medications were used in combinations, and 7 patients became seizure-free, and most of them achieved seizure freedom within the first 2 years of life irrespective of the type of the mutation. Effective medications for the seizure-free individuals included adrenocorticotropic (ACTH) and/or levetiracetam and/or phenobarbital and/or sodium valproate and/or topiramate and/or vigabatrin and/or nitrazepam. There was no correlation between the types of pathogenic variants and the phenotypes. Conclusion Our case-series showed that there is no genotype-phenotype correlation in patients with STXBP1-related disorders. This study adds 7 novel variants which expand the spectrum of STXBP1-related disorders. Combinations of levetiracetam and/or sodium valproate and/or ACTH and/or phenobarbital and/or vigabatrin and/or topiramate and/or nitrazepam were more often associated with seizure freedom in our cohort within 2 years of life. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1755-8794 |
| العلاقة: | https://doaj.org/toc/1755-8794Test |
| DOI: | 10.1186/s12920-023-01474-2 |
| الوصول الحر: | https://doaj.org/article/4821c7eafb7f43a99499e170e8ba1a51Test |
| رقم الانضمام: | edsdoj.4821c7eafb7f43a99499e170e8ba1a51 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17558794 |
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| DOI: | 10.1186/s12920-023-01474-2 |