Case Report: A Novel Intronic Mutation in AIFM1 Associated With Fatal Encephalomyopathy and Mitochondrial Disease in Infant

Qi Peng; Keze Ma; Linsheng Wang; Yinghua Zhu; Yaozhong Zhang; Chunbao Rao; Dong Luo; Zaixue Jiang; Wei Lai; Huiling Lu; Chaohui Duan; Zhongjun Zhou; Xiaomei Lu

doi:10.3389/fped.2022.889089

Case Report: A Novel Intronic Mutation in AIFM1 Associated With Fatal Encephalomyopathy and Mitochondrial Disease in Infant

Front Pediatr. 2022 May 31:10:889089. doi: 10.3389/fped.2022.889089. eCollection 2022.

Authors

Qi Peng^{1

2

3}, Keze Ma⁴, Linsheng Wang⁵, Yinghua Zhu^{1

2

3}, Yaozhong Zhang^{1

2

3}, Chunbao Rao^{2

3}, Dong Luo^{2

3}, Zaixue Jiang^{2

3}, Wei Lai⁶, Huiling Lu⁴, Chaohui Duan⁷, Zhongjun Zhou⁵, Xiaomei Lu^{1

2

3}

Affiliations

¹ Laboratory Department, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China.
² Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China.
³ Key Laboratory for Children's Genetics and Infectious Diseases of Dongguan, Dongguan, China.
⁴ Pediatric Intensive Care Unit, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China.
⁵ School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
⁶ Department of Radiology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China.
⁷ Laboratory of Clinical, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Abstract

Background: The AIFM1 gene is located on chromosome Xq26.1 and encodes a flavoprotein essential for nuclear disassembly in apoptotic cells. Mutations in this gene can cause variable clinical phenotypes, but genotype-phenotype correlations of AIFM1-related disorder have not yet been fully determined because of the clinical scarcity.

Case presentation: We describe a 4-month-old infant with mitochondrial encephalopathy, carrying a novel intronic variant in AIFM1 (NM_004208.4: c.1164 + 5G > A). TA cloning of the complementary DNA (cDNA) and Sanger sequencing revealed the simultaneous presence of an aberrant transcript with exon 11 skipping (89 bp) and a normal transcript through analysis of mRNA extracted from the patient's fibroblasts, which is consistent with direct RNA sequencing results.

Conclusion: We verified the pathogenic effect of the AIFM1 c.1164 + 5G > A splicing variant, which disturbed normal mRNA splicing. Our findings expand the mutation spectrum of AIFM1 and point out the necessity of intronic sequence analysis and the importance for integrative functional studies in the interpretation of sequence variants.

Keywords: AIFM1; fatal encephalomyopathy; mitochondrial disease; novel intronic mutation; whole-exome sequencing.

Publication types

Case Reports