دورية أكاديمية
Expanding the genetic spectrum of giant axonal neuropathy: Two novel variants in Iranian families.
العنوان: | Expanding the genetic spectrum of giant axonal neuropathy: Two novel variants in Iranian families. |
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المؤلفون: | Ashrafi MR; Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.; Department of Paediatrics, Division of Paediatric Neurology, Growth and Development Research Center, Children's Medical Centre, Paediatrics Centre of Excellence, Tehran University of Medical Sciences, Tehran, Iran., Dehnavi AZ; Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran., Tavasoli AR; Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.; Myelin Disorders Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.; Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA., Heidari M; Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.; Myelin Disorders Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran., Ghahvechi Akbari M; Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.; Physical Medicine and Rehabilitation department, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., Ronagh AR; Pediatric Neurology Department, Alborz University of Medical Sciences, Karaj, Iran., Ghafouri M; Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran., Mahdieh N; Genetic Research Center, Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran., Mohammadi P; Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.; Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran., Rezaei Z; Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. |
المصدر: | Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2023 Jun; Vol. 11 (6), pp. e2159. Date of Electronic Publication: 2023 Mar 03. |
نوع المنشور: | Case Reports; Review; Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: John Wiley & Sons Country of Publication: United States NLM ID: 101603758 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2324-9269 (Electronic) Linking ISSN: 23249269 NLM ISO Abbreviation: Mol Genet Genomic Med Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Hoboken, NJ] : John Wiley & Sons, [2013]- |
مواضيع طبية MeSH: | Giant Axonal Neuropathy*/diagnosis , Giant Axonal Neuropathy*/genetics , Giant Axonal Neuropathy*/pathology , Peripheral Nervous System Diseases*/genetics, Male ; Humans ; Child ; Iran ; Retrospective Studies ; Cytoskeletal Proteins/genetics ; Mutation |
مستخلص: | Background: Giant axonal neuropathy (GAN) is a progressive childhood hereditary polyneuropathy that affects both the peripheral and central nervous systems. Disease-causing variants in the gigaxonin gene (GAN) cause autosomal recessive giant axonal neuropathy. Facial weakness, nystagmus, scoliosis, kinky or curly hair, pyramidal and cerebellar signs, and sensory and motor axonal neuropathy are the main symptoms of this disorder. Here, we report two novel variants in the GAN gene from two unrelated Iranian families. Methods: Clinical and imaging data of patients were recorded and evaluated, retrospectively. Whole-exome sequencing (WES) was undertaken in order to detect disease-causing variants in participants. Confirmation of a causative variant in all three patients and their parents was carried out using Sanger sequencing and segregation analysis. In addition, for comparing to our cases, we reviewed all relevant clinical data of previously published cases of GAN between the years 2013-2020. Results: Three patients from two unrelated families were included. Using WES, we identified a novel nonsense variant [NM_022041.3:c.1162del (p.Leu388Ter)], in a 7-year-old boy of family 1, and a likely pathogenic missense variant [NM_022041.3:c.370T>A (p.Phe124Ile)], in two affected siblings of the family 2. Clinical examination revealed typical features of GAN-1 in all three patients, including walking difficulties, ataxic gait, kinky hair, sensory-motor polyneuropathy, and nonspecific neuroimaging abnormalities. Review of 63 previously reported cases of GAN indicated unique kinky hair, gait problem, hyporeflexia/areflexia, and sensory impairment were the most commonly reported clinical features. Conclusions: One homozygous nonsense variant and one homozygous missense variant in the GAN gene were discovered for the first time in two unrelated Iranian families that expand the mutation spectrum of GAN. Imaging findings are nonspecific, but the electrophysiological study in addition to history is helpful to achieve the diagnosis. The molecular test confirms the diagnosis. (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.) |
References: | Acta Neurol Belg. 2022 Oct;122(5):1201-1210. (PMID: 34120322) Acta Neurol Belg. 2021 Feb;121(1):143-151. (PMID: 33175337) Mol Genet Genomic Med. 2023 Jun;11(6):e2159. (PMID: 36866531) Hum Genet. 2016 Jul;135(7):675-84. (PMID: 27023907) Ann Indian Acad Neurol. 2018 Oct-Dec;21(4):304-308. (PMID: 30532362) Bioinformatics. 2015 Dec 15;31(24):4003-5. (PMID: 26323715) Medicine (Baltimore). 2015 Nov;94(44):e1749. (PMID: 26554773) Brain Dev. 2015 Sep;37(8):803-7. (PMID: 25533284) Prep Biochem Biotechnol. 2017 Aug 9;47(7):703-708. (PMID: 28277822) Brain Dev. 2016 Mar;38(3):350-3. (PMID: 26381321) Front Neurosci. 2020 Feb 25;14:85. (PMID: 32158379) Can J Neurol Sci. 2014 Nov;41(6):777-9. (PMID: 26693541) Nucleic Acids Res. 2016 Jul 8;44(W1):W344-50. (PMID: 27166375) Neuromuscul Disord. 2014 Jan;24(1):48-55. (PMID: 23890932) Clin Genet. 2015 Apr;87(4):395-7. (PMID: 25040701) Cold Spring Harb Perspect Biol. 2017 Apr 3;9(4):. (PMID: 28373358) Neurology. 2014 Mar 4;82(9):816-7. (PMID: 24590247) Muscle Nerve. 2014 Aug;50(2):200-5. (PMID: 24273072) Genome Biol. 2016 Jun 06;17(1):122. (PMID: 27268795) World J Pediatr. 2018 Jun;14(3):298-304. (PMID: 29876741) Clin Chim Acta. 2020 Mar;502:91-98. (PMID: 31877298) Mol Ther Methods Clin Dev. 2018 Feb 15;9:160-171. (PMID: 29766026) BMJ Case Rep. 2014 Sep 12;2014:. (PMID: 25216920) Curr Biol. 2005 Nov 22;15(22):2050-5. (PMID: 16303566) J Cell Biol. 2002 Aug 5;158(3):427-33. (PMID: 12147674) J Child Neurol. 2015 Jun;30(7):912-5. (PMID: 25213662) Eur J Paediatr Neurol. 2013 May;17(3):259-64. (PMID: 23332420) Mol Genet Genomic Med. 2021 Nov;9(11):e1834. (PMID: 34636477) Arch Pediatr. 2018 Nov;25(8):452-458. (PMID: 30340945) Turk J Pediatr. 2019;61(2):275-278. (PMID: 31951341) BMC Med Genet. 2016 Nov 16;17(1):82. (PMID: 27852232) Neurology. 2014 Mar 11;82(10):873-8. (PMID: 24500646) J Biol Chem. 2005 Aug 26;280(34):30091-9. (PMID: 15983046) Mol Biol Cell. 2016 Feb 15;27(4):608-16. (PMID: 26700320) Genet Med. 2015 May;17(5):405-24. (PMID: 25741868) J Clin Neurosci. 2014 May;21(5):865-7. (PMID: 24211141) Handb Clin Neurol. 2013;115:933-8. (PMID: 23931822) Orphanet J Rare Dis. 2019 Feb 1;14(1):27. (PMID: 30709364) Neuroophthalmology. 2013 Sep 24;37(5):209-213. (PMID: 28167990) Hum Gene Ther. 2013 Feb;24(2):209-19. (PMID: 23316953) Neurogenetics. 2020 Jan;21(1):29-37. (PMID: 31655922) Nature. 2005 Nov 10;438(7065):224-8. (PMID: 16227972) Brain Dev. 2012 Feb;34(2):156-62. (PMID: 21356581) An Bras Dermatol. 2016 Sep-Oct;91(5 suppl 1):125-127. (PMID: 28300918) Am J Med Genet A. 2010 Nov;152A(11):2802-4. (PMID: 20949505) Evol Bioinform Online. 2018 Mar 12;14:1176934318760543. (PMID: 29568218) Muscle Nerve. 2014 Oct;50(4):467-76. (PMID: 24947478) BMJ Open. 2018 Oct 28;8(10):e021632. (PMID: 30373780) Nat Genet. 2000 Nov;26(3):370-4. (PMID: 11062483) Chin Med J (Engl). 2018 Oct 5;131(19):2371-2372. (PMID: 30246730) J Peripher Nerv Syst. 2012 Jun;17(2):210-6. (PMID: 22734908) Hum Mol Genet. 2016 Jun 1;25(11):2143-2157. (PMID: 27000625) Am J Med Genet A. 2022 Mar;188(3):836-846. (PMID: 34889507) |
معلومات مُعتمدة: | 971846 NIMAD |
فهرسة مساهمة: | Keywords: Giant Axonal Neuropathy; WES; gigaxonin |
المشرفين على المادة: | 0 (Cytoskeletal Proteins) |
تواريخ الأحداث: | Date Created: 20230303 Date Completed: 20230615 Latest Revision: 20230616 |
رمز التحديث: | 20230616 |
مُعرف محوري في PubMed: | PMC10265088 |
DOI: | 10.1002/mgg3.2159 |
PMID: | 36866531 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2324-9269 |
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DOI: | 10.1002/mgg3.2159 |