Case Report: Compound Heterozygous Variants in Identified in a Chinese Infant With Molybdenum Cofactor Deficiency

Overview

Journal Front Genet

Date 2021 Apr 26

PMID 33897766

Citations 4

Authors

Qi Tian

Yang Cao

Li Shu

Yongjun Chen

Ying Peng

Yaqin Wang

Yuanyuan Chen

Hua Wang

Xiao Mao

Affiliations

Soon will be listed here.

Abstract

The molybdenum cofactor (Moco) deficiency in humans results in the inactivity of molybdenum-dependent enzymes and is caused by pathogenic variants in (), (), and (). These genes along with () are involved in Moco biosynthesis and providing cofactors to Moco-dependent enzymes. Until now, there was no study to confirm that is a causative gene of Moco deficiency. Detailed clinical information was collected in the pedigree. The Whole-exome sequencing (WES) accompanied with Sanger sequencing validation were performed. We described the clinical presentations of an infant, born to a non-consanguineous healthy family, diagnosed as having variants caused Moco deficiency and showing typical features of Moco deficiency including severe neurologic symptoms and cystic encephalomalacia in the brain MRI, resulting in neonatal death. Compound heterozygous variants in the gene were identified by WES. Positive sulfite and decreased levels of uric acid in plasma and urine were detected. To our knowledge, this is the first case of variants causing Moco deficiency. Our study may contribute to genetic diagnosis of Moco deficiency and future genetic counseling.

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References

Arican P, Gencpinar P, Kirbiyik O, Bozkaya Yilmaz S, Ersen A, Oztekin O . The Clinical and Molecular Characteristics of Molybdenum Cofactor Deficiency Due to MOCS2 Mutations. Pediatr Neurol. 2019; 99:55-59. DOI: 10.1016/j.pediatrneurol.2019.04.021. View

Yoganathan S, Sudhakar S, Thomas M, Dutta A, Danda S, Chandran M . Novel Imaging Finding and Novel Mutation in an Infant with Molybdenum Cofactor Deficiency, a Mimicker of Hypoxic-Ischaemic Encephalopathy. Iran J Child Neurol. 2018; 12(2):107-112. PMC: 5904745. View

Tessarech M, Gorce M, Boussion F, Bault J, Triau S, Charif M . Second report of RING finger protein 113A (RNF113A) involvement in a Mendelian disorder. Am J Med Genet A. 2019; 182(3):565-569. DOI: 10.1002/ajmg.a.61384. View

Bender D, Kaczmarek A, Angel Santamaria-Araujo J, Stueve B, Waltz S, Bartsch D . Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. Hum Mol Genet. 2019; 28(17):2885-2899. DOI: 10.1093/hmg/ddz109. View

Rentzsch P, Witten D, Cooper G, Shendure J, Kircher M . CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 2018; 47(D1):D886-D894. PMC: 6323892. DOI: 10.1093/nar/gky1016. View

Stockley J, Morgan N, Bem D, Lowe G, Lordkipanidze M, Dawood B . Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects. Blood. 2013; 122(25):4090-3. PMC: 3862284. DOI: 10.1182/blood-2013-06-506873. View

Plate J, Sassen W, Hassan A, Lehne F, Koster R, Kruse T . S-Sulfocysteine Induces Seizure-Like Behaviors in Zebrafish. Front Pharmacol. 2019; 10:122. PMC: 6454129. DOI: 10.3389/fphar.2019.00122. View

Shihab H, Gough J, Cooper D, Stenson P, Barker G, Edwards K . Predicting the functional, molecular, and phenotypic consequences of amino acid substitutions using hidden Markov models. Hum Mutat. 2012; 34(1):57-65. PMC: 3558800. DOI: 10.1002/humu.22225. View

Atwal P, Scaglia F . Molybdenum cofactor deficiency. Mol Genet Metab. 2015; 117(1):1-4. DOI: 10.1016/j.ymgme.2015.11.010. View

10.

Markus F, Angelini C, Trimouille A, Rudolf G, Lesca G, Goizet C . Rare variants in the GABA receptor subunit ε identified in patients with a wide spectrum of epileptic phenotypes. Mol Genet Genomic Med. 2020; 8(9):e1388. PMC: 7507344. DOI: 10.1002/mgg3.1388. View

11.

Marelja Z, Leimkuhler S, Missirlis F . Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Life Cycle by Controlling Cell Metabolism. Front Physiol. 2018; 9:50. PMC: 5817353. DOI: 10.3389/fphys.2018.00050. View

12.

Neukranz Y, Kotter A, Beilschmidt L, Marelja Z, Helm M, Graf R . Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-Independent Localization of NFS1 at the Tips of the Centrosome. Biochemistry. 2019; 58(13):1786-1798. DOI: 10.1021/acs.biochem.8b01160. View

13.

Huijmans J, Schot R, de Klerk J, Williams M, de Coo R, Duran M . Molybdenum cofactor deficiency: Identification of a patient with homozygote mutation in the MOCS3 gene. Am J Med Genet A. 2017; 173(6):1601-1606. DOI: 10.1002/ajmg.a.38240. View

14.

Zaki M, Selim L, El-Bassyouni H, Issa M, Mahmoud I, Ismail S . Molybdenum cofactor and isolated sulphite oxidase deficiencies: Clinical and molecular spectrum among Egyptian patients. Eur J Paediatr Neurol. 2016; 20(5):714-22. PMC: 4993451. DOI: 10.1016/j.ejpn.2016.05.011. View

15.

Wang K, Li M, Hakonarson H . ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010; 38(16):e164. PMC: 2938201. DOI: 10.1093/nar/gkq603. View

16.

Mayr S, Mendel R, Schwarz G . Molybdenum cofactor biology, evolution and deficiency. Biochim Biophys Acta Mol Cell Res. 2020; 1868(1):118883. DOI: 10.1016/j.bbamcr.2020.118883. View

17.

Shihab H, Gough J, Cooper D, Day I, Gaunt T . Predicting the functional consequences of cancer-associated amino acid substitutions. Bioinformatics. 2013; 29(12):1504-10. PMC: 3673218. DOI: 10.1093/bioinformatics/btt182. View

18.

Reiss J, Johnson J . Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH. Hum Mutat. 2003; 21(6):569-76. DOI: 10.1002/humu.10223. View

19.

Schwarz J, Cooper D, Schuelke M, Seelow D . MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods. 2014; 11(4):361-2. DOI: 10.1038/nmeth.2890. View

20.

Kircher M, Witten D, Jain P, ORoak B, Cooper G, Shendure J . A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014; 46(3):310-5. PMC: 3992975. DOI: 10.1038/ng.2892. View