AUTHOR=Yang Yue , Zhang Shijie , Yang Wenming , Wei Taohua , Hao Wenjie , Cheng Ting , Wang Jiuxiang , Dong Wei , Qian Nannan 

TITLE=Case Report: Identification of a De novo C19orf12 Variant in a Patient With Mitochondrial Membrane Protein–Associated Neurodegeneration

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.852374

DOI=10.3389/fgene.2022.852374

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Mitochondrial membrane protein–associated neurodegeneration (MPAN) mostly arises as an autosomal recessive disease and is caused by variants in the chromosome 19 open reading frame 12 (<italic>C19orf12</italic>) gene. However, a few <italic>C19orf12</italic> monoallelic truncating <italic>de novo</italic> variants have been reported and segregated as autosomal dominant traits in some cases.</p><p><bold>Methods:</bold> We performed whole-exome sequencing and analyzed genes related to neurodegeneration associated with brain iron accumulation for pathogenic variants. The identified variants were confirmed by Sanger sequencing and tested using <italic>in silico</italic> tools.</p><p><bold>Results:</bold> The patient had an onset of depression at the age of 22 years, which rapidly progressed to severe dystonia, dementia, and bladder and bowel incontinence. Neuroimaging showed hypointensity in the substantia nigra and the globus pallidum, with additional frontotemporal atrophy. Genetic analysis revealed a single complex <italic>de novo</italic> variant [c.336_338delinsCACA (p.Trp112CysfsTer40)] in the <italic>C19orf12</italic> gene.</p><p><bold>Conclusion:</bold> This study enriches the genetic spectrum and clinical features of <italic>C19orf12</italic> variants and provides additional evidence of the variable inheritance pattern of MPAN.</p>