Leigh syndrome associated with a novel mutation in the COX15 gene
-
Mohammad Miryounesi
Abstract
Leigh syndrome (LS) is a subacute necrotizing encephalomyelopathy with a diverse range of symptoms, such as psychomotor delay or regression, weakness, hypotonia, truncal ataxia, intention tremor as well as lactic acidosis in the blood, cerebrospinal fluid or urine. Both nuclear gene defects and mutations of the mitochondrial genome have been detected in these patients. Here we report a 7-year-old girl with hypotonia, tremor, developmental delay and psychomotor regression. However, serum lactate level as well as brain magnetic resonance imaging were normal. Mutational analysis has revealed a novel mutation in exon 4 of COX15 gene (c.415C>G) which results in p.Leu139Val. Previous studies have demonstrated that COX15 mutations are associated with typical LS as well as fatal infantile hypertrophic cardiomyopathy. Consequently, clinical manifestations of COX15 mutations may be significantly different in patients. Such information is of practical importance in genetic counseling.
Correction note:
Correction added after online publication March 9, 2016: Mistakenly this article was previously published online ahead of print containing wrong names for 2 authors: Majid Faraei, Seyed Mohammad Bagher Tabei.
The correct names are: Majid Fardaei, Seyed Mohammadbagher Tabei.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Ronchi D, Cosi A, Tonduti D, Orcesi S, Bordoni A, et al. Clinical and molecular features of an infant patient affected by Leigh Disease associated to m.14459G>A mitochondrial DNA mutation: a case report. BMC Neurol 2011;11:85.10.1186/1471-2377-11-85Search in Google Scholar PubMed PubMed Central
2. Rocha V, Rocha D, Santos H, Marques JS. Growth hormone deficiency in a patient with mitochondrial disease. J Pediatr Endocr Met 2015;28:1003–4.10.1515/jpem-2014-0315Search in Google Scholar PubMed
3. Ozmen E, Unlu HA, Demirkan TH, Tiftik M, Adaletli I. Radiologic manifestation of a BCS1L-mutated patient. J Pediatr Endocr Met 2014;27:363–5.Search in Google Scholar
4. Taylor RW, Morris AA, Hutchinson M, Turnbull DM. Leigh disease associated with a novel mitochondrial DNA ND5 mutation. Eur J Hum Genet 2002;10:141–4.10.1038/sj.ejhg.5200773Search in Google Scholar PubMed
5. Lake NJ, Compton AG, Rahman S, Thorburn DR. Leigh syndrome: one disorder, more than 75 monogenic causes. Ann Neurol 2016;79:190–203.10.1002/ana.24551Search in Google Scholar PubMed
6. Oquendo C, Antonicka H, Shoubridge E, Reardon W, Brown G. Functional and genetic studies demonstrate that mutation in the COX15 gene can cause Leigh syndrome. J Med Genet 2004;41:540–4.10.1136/jmg.2003.017426Search in Google Scholar PubMed PubMed Central
7. Petruzzella V, Tiranti V, Fernandez P, Ianna P, Carrozzo R, et al. Identification and characterization of human cDNAs specific to BCS1, PET112, SCO1, COX15, and COX11, five genes involved in the formation and function of the mitochondrial respiratory chain. Genomics 1998;54:494–504.10.1006/geno.1998.5580Search in Google Scholar PubMed
8. Shrikhande DY, Kalakoti P, Syed MA, Ahya K, Singh G. A rare mitochondrial disorder: leigh sydrome. Ital J Pediatr 2010;36:622010.10.1186/1824-7288-36-62Search in Google Scholar PubMed PubMed Central
9. Arii J, Tanabe Y. Leigh syndrome: serial MR imaging and clinical follow-up. AJNR. Am J Neuroradiol 2000;21:1502–9.Search in Google Scholar
10. Wortmann SB, Koolen DA, Smeitink JA, van den Heuvel L, Rodenburg RJ. Whole exome sequencing of suspected mitochondrial patients in clinical practice. J Inherit Metab Dis 2015;38:437–43.10.1007/s10545-015-9823-ySearch in Google Scholar PubMed PubMed Central
11. Tetreault M, Fahiminiya S, Antonicka H, Mitchell GA, Geraghty MT, et al. Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome. Hum Genet 2015;134: 981–91.10.1007/s00439-015-1577-ySearch in Google Scholar PubMed
12. Antonicka H, Mattman A, Carlson CG, Glerum DM, Hoffbuhr KC, et al. Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy. Am J Hum Genet 2003;72: 101–14.10.1086/345489Search in Google Scholar PubMed PubMed Central
13. Bugiani M, Tiranti V, Farina L, Uziel G,Zeviani M. Novel mutations in COX15 in a long surviving Leigh syndrome patient with cytochrome c oxidase deficiency. J Med Genet 2005;42:e28.10.1136/jmg.2004.029926Search in Google Scholar PubMed PubMed Central
14. Alfadhel M, Lillquist YP, Waters PJ, Sinclair G, Struys E, et al. Infantile cardioencephalopathy due to a COX15 gene defect: report and review. Am J Med Genet A 2011;155A:840–4.10.1002/ajmg.a.33881Search in Google Scholar PubMed
©2016 by De Gruyter
Articles in the same Issue
- Frontmatter
- Review
- Medullary thyroid carcinoma: a review on ethical considerations in treatment of children
- Original Articles
- Monocyte chemoattractant protein 1 and macrophage migration inhibitory factor in children with type 1 diabetes
- Organ-specific autoimmunity in relation to clinical characteristics in children with long-lasting type 1 diabetes
- Seasonality of diagnosis of type 1 diabetes mellitus in the Netherlands (Young Dudes-2)
- Health-related quality of life in children and adolescents with type 1 diabetes mellitus from Montenegro: relationship to metabolic control
- Relation of fetuin A levels with cardiac, subcutaneous lipid accumulation and insulin resistance parameters in Turkish obese children
- Prooxidant-antioxidant balance in patients with phenylketonuria and its correlation to biochemical and hematological parameters
- Serum vaspin concentrations in girls with anorexia nervosa
- Effect of intramuscular cholecalciferol megadose in children with nutritional rickets
- Focus on BMI and subclinical hypothyroidism in adolescent girls first examined for amenorrhea or oligomenorrhea. The emerging role of polycystic ovary syndrome
- Absence of a relationship between thyroid hormones and vitamin D levels
- Parathyroid hormone-ionized calcium dynamics over the first year of life
- Biochemical markers of bone turnover in children with clinical bone fragility
- Adipocytokines and bone metabolism markers in relation to bone mineral values in early pubertal boys with different physical activity
- Bone mineral density in young Chilean patients with type 1 diabetes mellitus
- Case Reports
- A case of mature teratoma with a falsely high serum estradiol value measured with an immunoassay
- Leigh syndrome associated with a novel mutation in the COX15 gene
- More than one way to skin a thyroid. Managing pediatric hypothyroidism with weekly intramuscular levothyroxine
- First case report of rare congenital adrenal insufficiency caused by mutations in the CYP11A1 gene in the Czech Republic
- Arg924X homozygous mutation in insulin receptor gene in a Tunisian patient with Donohue syndrome
- Corrigendum
- Corrigendum to: Exposure to sunshine early in life prevented development of type 1 diabetes in Danish boys
Articles in the same Issue
- Frontmatter
- Review
- Medullary thyroid carcinoma: a review on ethical considerations in treatment of children
- Original Articles
- Monocyte chemoattractant protein 1 and macrophage migration inhibitory factor in children with type 1 diabetes
- Organ-specific autoimmunity in relation to clinical characteristics in children with long-lasting type 1 diabetes
- Seasonality of diagnosis of type 1 diabetes mellitus in the Netherlands (Young Dudes-2)
- Health-related quality of life in children and adolescents with type 1 diabetes mellitus from Montenegro: relationship to metabolic control
- Relation of fetuin A levels with cardiac, subcutaneous lipid accumulation and insulin resistance parameters in Turkish obese children
- Prooxidant-antioxidant balance in patients with phenylketonuria and its correlation to biochemical and hematological parameters
- Serum vaspin concentrations in girls with anorexia nervosa
- Effect of intramuscular cholecalciferol megadose in children with nutritional rickets
- Focus on BMI and subclinical hypothyroidism in adolescent girls first examined for amenorrhea or oligomenorrhea. The emerging role of polycystic ovary syndrome
- Absence of a relationship between thyroid hormones and vitamin D levels
- Parathyroid hormone-ionized calcium dynamics over the first year of life
- Biochemical markers of bone turnover in children with clinical bone fragility
- Adipocytokines and bone metabolism markers in relation to bone mineral values in early pubertal boys with different physical activity
- Bone mineral density in young Chilean patients with type 1 diabetes mellitus
- Case Reports
- A case of mature teratoma with a falsely high serum estradiol value measured with an immunoassay
- Leigh syndrome associated with a novel mutation in the COX15 gene
- More than one way to skin a thyroid. Managing pediatric hypothyroidism with weekly intramuscular levothyroxine
- First case report of rare congenital adrenal insufficiency caused by mutations in the CYP11A1 gene in the Czech Republic
- Arg924X homozygous mutation in insulin receptor gene in a Tunisian patient with Donohue syndrome
- Corrigendum
- Corrigendum to: Exposure to sunshine early in life prevented development of type 1 diabetes in Danish boys
