Top

Published in:

Open Access 01-12-2024 | Disorders of Intellectual Development | Case Report

The first case of intellectual disability caused by novel compound heterozygosity for NUDT2 variants

Authors: Bo Bi, Xiaohong Chen, Shan Huang, Min Peng, Weiyue Gu, Hongmin Zhu, Yangcan Ming

Published in: BMC Pediatrics | Issue 1/2024

Abstract

NUDT2 is an enzyme important for maintaining the intracellular level of the diadenosine tetraphosphate (Ap4A). Bi-allelic loss of function variants in NUDT2 has recently been reported as a rare cause of intellectual disability (ID). Herein, we describe a Chinese girl with ID, attention deficit hyperactivity disorder (ADHD), and motor delays with abnormal walking posture and difficulty climbing stairs, who bears compound heterozygous variants c.34 C > T (p.R12*) and c.194T > G (p.I65R) in NUDT2. Homozygous variants c.34 C > T (p.R12*) or c.186del (p.A63Qfs*3) in NUDT2 were previously reported to cause ID. This is the first patient with ID due to compound heterozygous variants in NUDT2 and p.I65R is a novel missense variant. This study enriched the genotype and phenotype of NUDT2-related ID and supported the critical developmental involvement of NUDT2.

Vasudevan P, Suri M. A clinical approach to developmental delay and intellectual disability. Clin Med (Lond). 2017;17(6):558–61. https://doi.org/10.7861/clinmedicine.17-6-558.CrossRefPubMed

Bass N, Skuse D. Genetic testing in children and adolescents with intellectual disability. Curr Opin Psychiatry. 2018;31(6):490–5. https://doi.org/10.1097/YCO.0000000000000456.CrossRefPubMed

Laudenbach BT, Krey K, Emslander Q, et al. NUDT2 initiates viral RNA degradation by removal of 5’-phosphates. Nat Commun. 2021;12(1):6918. https://doi.org/10.1038/s41467-021-27239-y.CrossRefPubMedPubMedCentral

Sharma S, Grudzien-Nogalska E, Hamilton K, et al. Mammalian nudix proteins cleave nucleotide metabolite caps on RNAs. Nucleic Acids Res. 2020;48(12):6788–98. https://doi.org/10.1093/nar/gkaa402.CrossRefPubMedPubMedCentral

Kwon O, Kwak D, Ha SH, et al. Nudix-type motif 2 contributes to cancer proliferation through the regulation of rag GTPase-mediated mammalian target of rapamycin complex 1 localization. Cell Signal. 2017;32:24–35. https://doi.org/10.1016/j.cellsig.2017.01.015.CrossRefPubMed

Marriott AS, Vasieva O, Fang Y, Copeland NA, McLennan AG, Jones NJ. NUDT2 disruption elevates Diadenosine Tetraphosphate (Ap4A) and down-regulates Immune Response and Cancer Promotion genes. PLoS ONE. 2016;11(5):e0154674. https://doi.org/10.1371/journal.pone.0154674.CrossRefPubMedPubMedCentral

Oka K, Suzuki T, Onodera Y, et al. Nudix-type motif 2 in human breast carcinoma: a potent prognostic factor associated with cell proliferation. Int J Cancer. 2011;128(8):1770–82. https://doi.org/10.1002/ijc.25505.CrossRefPubMed

Anazi S, Maddirevula S, Faqeih E, et al. Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield. Mol Psychiatry. 2017;22(4):615–24. https://doi.org/10.1038/mp.2016.113.CrossRefPubMed

Yavuz H, Bertoli-Avella AM, Alfadhel M, et al. A founder nonsense variant in NUDT2 causes a recessive neurodevelopmental disorder in Saudi arab children. Clin Genet. 2018;94(3–4):393–5. https://doi.org/10.1111/cge.13386.CrossRefPubMed

10.

Diaz F, Khosa S, Niyazov D, et al. Novel NUDT2 variant causes intellectual disability and polyneuropathy. Ann Clin Transl Neurol. 2020;7(11):2320–5. https://doi.org/10.1002/acn3.51209.CrossRefPubMedPubMedCentral

11.

Lee H, Huang AY, Wang LK, et al. Diagnostic utility of transcriptome sequencing for rare mendelian diseases. Genet Med. 2020;22(3):490–9. https://doi.org/10.1038/s41436-019-0672-1.CrossRefPubMed

12.

MacArthur DG, Manolio TA, Dimmock DP, et al. Guidelines for investigating causality of sequence variants in human disease. Nature. 2014;508(7497):469–76. https://doi.org/10.1038/nature13127.CrossRefPubMedPubMedCentral

13.

Li H, Durbin R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics. 2010;26(5):589–95. https://doi.org/10.1093/bioinformatics/btp698.CrossRefPubMedPubMedCentral

14.

McKenna A, Hanna M, Banks E, et al. The genome analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20(9):1297–303. https://doi.org/10.1101/gr.107524.110.CrossRefPubMedPubMedCentral

15.

Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24. https://doi.org/10.1038/gim.2015.30.CrossRefPubMedPubMedCentral

Title: The first case of intellectual disability caused by novel compound heterozygosity for NUDT2 variants
Authors: Bo Bi
Xiaohong Chen
Shan Huang
Min Peng
Weiyue Gu
Hongmin Zhu
Yangcan Ming
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Disorders of Intellectual Development
Intellectual Disability
Attention Deficit Hyperactivity Disorder
Attention Deficit Hyperactivity Disorder
Published in: BMC Pediatrics / Issue 1/2024
Electronic ISSN: 1471-2431
DOI: https://doi.org/10.1186/s12887-024-04542-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The first case of intellectual disability caused by novel compound heterozygosity for NUDT2 variants

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2024

Sleep initiation patterns and sleep quality among toddlers in the southeast of China: initial study results

Parental engagement in research on paediatric lower respiratory tract infections in Indonesia

A review of the current policies and guidance regarding Apgar scoring and the detection of jaundice and cyanosis concerning Black, Asian and ethnic minority neonates

From variant of uncertain significance to likely pathogenic in two siblings with atypical RAG2 Deficiency: a case report and review of the literature

Nutritional support during the first week for infants with bronchopulmonary dysplasia and respiratory distress: a multicenter cohort study in China

Characterization of newly diagnosed type 1 diabetes in children and adolescents from 2017 to 2022 in China: a single-center analysis