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Unfolding of Novel Independent Missense Mutations in VAMP2 and AGRN and Their Collective Role in Global Developmental Delay: A Case Report.

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العنوان: Unfolding of Novel Independent Missense Mutations in VAMP2 and AGRN and Their Collective Role in Global Developmental Delay: A Case Report.
المؤلفون: Heidarpour N; Department of Basic Biomedical Sciences, Touro College of Osteopathic Medicine (TouroCOM), Middletown, USA., Singh A; Department of Basic Biomedical Sciences, Rutgers New Jersey Medical School, Newark, USA., Caputo JM; Department of Basic Biomedical Sciences, Touro College of Osteopathic Medicine (TouroCOM), Middletown, USA., Barbieri R; Department of Basic Biomedical Sciences, Touro College of Osteopathic Medicine (TouroCOM), Middletown, USA., Pampana VS; Department of Neurology, Middletown Medical, Middletown, USA., Kamath VG; Department of Basic Biomedical Sciences, Touro College of Osteopathic Medicine (TouroCOM), Middletown, USA., Kaur G; Department of Basic Biomedical Sciences, Touro College of Osteopathic Medicine (TouroCOM), Middletown, USA.
المصدر: Cureus [Cureus] 2022 Aug 27; Vol. 14 (8), pp. e28464. Date of Electronic Publication: 2022 Aug 27 (Print Publication: 2022).
نوع المنشور: Case Reports
اللغة: English
بيانات الدورية: Publisher: Cureus, Inc Country of Publication: United States NLM ID: 101596737 Publication Model: eCollection Cited Medium: Print ISSN: 2168-8184 (Print) Linking ISSN: 21688184 NLM ISO Abbreviation: Cureus Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Palo Alto, CA : Cureus, Inc.
مستخلص: Vesicle-associated membrane protein 2 ( VAMP2 ) and Agrin ( AGRN ) are crucial proteins in neurotransmission. VAMP2 is a vesicular protein that facilitates the exocytosis of neurotransmitters. At the same time, AGRN plays a critical role in the maintenance and function of neuromuscular junctions. Mutations in the signaling pathway of VAMP2 and AGRN impair proper signaling between the presynaptic and postsynaptic neurons, and can result in neurodevelopmental conditions known as global developmental delay (GDD). This study highlights a presentation of GDD in a patient with concurrent mutations in  VAMP2  and  AGRN . A three-year-old female child presented with GDD characterized by hypotonia, intellectual disability, and dysphagia. Physical exam exhibited signs of developmental delay and severe muscle weakness. EEG findings were suggestive of a hypsarrhythmia pattern. The ophthalmological evaluation showed partial optic atrophy bilaterally. Therapeutic interventions included Keppra and Topamax, which proved ineffective. The patient's outcome was inconclusive as care was transferred to another facility. This case study reports the novel appearance of two concurrent mutations: p.Gln76Pro associated with  VAMP2  and p.Gln970Glu associated with  AGRN . Mutations in  VAMP2  lead to a dysfunctional SNARE complex and inhibit exocytosis of neurotransmitters into the synaptic cleft. Mutations in  AGRN  impair the ability to form and activate postsynaptic nicotinic acetylcholine receptors. Improper signaling between presynaptic and postsynaptic neurons is an important determinant of GDD. We hope that accounting for this mutational pattern will contribute to understanding synapse assembly and help unravel the complex interplay of factors involved in the pathology of neuromuscular disorders and GDD.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright © 2022, Heidarpour et al.)
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فهرسة مساهمة: Keywords: agrin (agrn); congenital myasthenic syndrome (cms); global developmental delay (gdd); soluble n-ethylmaleimide-sensitive- factor attachment receptor (snare); vesicle associated membrane protein 2 (vamp2/synaptobrevin2)
تواريخ الأحداث: Date Created: 20220930 Latest Revision: 20221001
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC9511814
DOI: 10.7759/cureus.28464
PMID: 36176870
قاعدة البيانات: MEDLINE
الوصف
تدمد:2168-8184
DOI:10.7759/cureus.28464