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

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

JOURNAL=Frontiers in Pediatrics

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.889089

DOI=10.3389/fped.2022.889089

ISSN=2296-2360

ABSTRACT=<sec><title>Background</title><p>The <italic>AIFM1</italic> 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 <italic>AIFM1</italic>-related disorder have not yet been fully determined because of the clinical scarcity.</p></sec><sec><title>Case Presentation</title><p>We describe a 4-month-old infant with mitochondrial encephalopathy, carrying a novel intronic variant in <italic>AIFM1</italic> (NM_004208.4: c.1164 + 5G &gt; 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.</p></sec><sec><title>Conclusion</title><p>We verified the pathogenic effect of the <italic>AIFM1</italic> c.1164 + 5G &gt; A splicing variant, which disturbed normal mRNA splicing. Our findings expand the mutation spectrum of <italic>AIFM1</italic> and point out the necessity of intronic sequence analysis and the importance for integrative functional studies in the interpretation of sequence variants.</p></sec>