A description of novel variants and review of phenotypic spectrum in UBA5-related early epileptic encephalopathy
| العنوان: | A description of novel variants and review of phenotypic spectrum in UBA5-related early epileptic encephalopathy |
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| المؤلفون: | David A. Sweetser, Nutan Sharma, Elly Brokamp, Melissa A. Walker, Lisa G. Riley, Shekeeb S. Mohammad, Russell C. Dale, Frances A. High, Ryosuke Ishimura, Lauren C. Briere, Yoshinobu Ichimura, Mary Koziura, Cynthia M. Cooper, Masaaki Komatsu, Paul A. Caruso, Cassandra A Rogers, Christine J Callahan, John A. Phillips |
| المصدر: | Molecular Case Studies. 7:a005827 |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Dystonia, Genetics, Epilepsy, Genotype, medicine, Missense mutation, General Medicine, Global developmental delay, Biology, medicine.disease, Compound heterozygosity, Gene, Phenotype |
| الوصف: | Early infantile epileptic encephalopathy-44 (EIEE44, MIM: 617132) is a previously described condition resulting from biallelic variants in UBA5, a gene involved in a ubiquitin-like post-translational modification system called UFMylation. Here we report five children from four families with biallelic pathogenic variants in UBA5. All five children presented with global developmental delay, epilepsy, axial hypotonia, appendicular hypertonia, and a movement disorder, including dystonia in four. Affected individuals in all four families have compound heterozygous pathogenic variants in UBA5. All have the recurrent mild c.1111G > A (p.Ala371Thr) variant in trans with a second UBA5 variant. One patient has the previously described c.562C > T (p. Arg188*) variant, two other unrelated patients have a novel missense variant, c.907T > C (p.Cys303Arg), and the two siblings have a novel missense variant, c.761T > C (p.Leu254Pro). Functional analyses demonstrate that both the p.Cys303Arg variant and the p.Leu254Pro variants result in a significant decrease in protein function. We also review the phenotypes and genotypes of all 15 previously reported families with biallelic UBA5 variants, of which two families have presented with distinct phenotypes, and we describe evidence for some limited genotype–phenotype correlation. The overlap of motor and developmental phenotypes noted in our cohort and literature review adds to the increasing understanding of genetic syndromes with movement disorders-epilepsy. |
| تدمد: | 2373-2873 2373-2865 |
| DOI: | 10.1101/mcs.a005827 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::b5a82de83066891e2ecb745b41807f83 https://doi.org/10.1101/mcs.a005827 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi...........b5a82de83066891e2ecb745b41807f83 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23732873 23732865 |
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| DOI: | 10.1101/mcs.a005827 |