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CACNA1A Mutations Causing Early Onset Ataxia: Profiling Clinical, Dysmorphic and Structural-Functional Findings

التفاصيل البيبلوغرافية
العنوان: CACNA1A Mutations Causing Early Onset Ataxia: Profiling Clinical, Dysmorphic and Structural-Functional Findings
المؤلفون: Antonio F. Martínez-Monseny, Albert Edo, Dídac Casas-Alba, Mercè Izquierdo-Serra, Mercè Bolasell, David Conejo, Loreto Martorell, Jordi Muchart, Laura Carrera, Carlos I. Ortez, Andrés Nascimento, Baldo Oliva, José M. Fernández-Fernández, Mercedes Serrano
المصدر: International Journal of Molecular Sciences, Vol 22, Iss 10, p 5180 (2021)
بيانات النشر: MDPI AG, 2021.
سنة النشر: 2021
المجموعة: LCC:Biology (General)
LCC:Chemistry
مصطلحات موضوعية: ataxia, cerebellar atrophy, dysmorphic traits, early-onset cerebellar ataxia, CACNA1A gene, CaV2.1 (P/Q-type) voltage-dependent calcium channel, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: The CACNA1A gene encodes the pore-forming α1A subunit of the voltage-gated CaV2.1 Ca2+ channel, essential in neurotransmission, especially in Purkinje cells. Mutations in CACNA1A result in great clinical heterogeneity with progressive symptoms, paroxysmal events or both. During infancy, clinical and neuroimaging findings may be unspecific, and no dysmorphic features have been reported. We present the clinical, radiological and evolutionary features of three patients with congenital ataxia, one of them carrying a new variant. We report the structural localization of variants and their expected functional consequences. There was an improvement in cerebellar syndrome over time despite a cerebellar atrophy progression, inconsistent response to acetazolamide and positive response to methylphenidate. The patients shared distinctive facial gestalt: oval face, prominent forehead, hypertelorism, downslanting palpebral fissures and narrow nasal bridge. The two α1A affected residues are fully conserved throughout evolution and among the whole human CaV channel family. They contribute to the channel pore and the voltage sensor segment. According to structural data analysis and available functional characterization, they are expected to exert gain- (F1394L) and loss-of-function (R1664Q/R1669Q) effect, respectively. Among the CACNA1A-related phenotypes, our results suggest that non-progressive congenital ataxia is associated with developmental delay and dysmorphic features, constituting a recognizable syndromic neurodevelopmental disorder.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1422-0067
1661-6596
Relation: https://www.mdpi.com/1422-0067/22/10/5180; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067
DOI: 10.3390/ijms22105180
URL الوصول: https://doaj.org/article/557b2a1eecf64bdeb4c9274c77b0e7cf
رقم الأكسشن: edsdoj.557b2a1eecf64bdeb4c9274c77b0e7cf
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14220067
16616596
DOI:10.3390/ijms22105180