[Pedigree analysis of C19ORF12 p.Asp18Tyr mutation in a family with mitochondrial membrane protein associated neurodegeneration].

Abstract

Objective: To explore the clinical features and analyze the chromosome 19 open reading frame 12(C19ORF12) gene mutation of a family with mitochondrial membrane protein-associated neurodegeneration (MPAN). Methods: The pedigree diagnosed as neurodegeneration with brain iron accumulation (NBIA) in Henan Provincial People s Hospital in May 2018 was collected, and clinical data of the patients in this family was further analyzed. Furthermore, whole exome sequencing (WES) was employed to identify the disease-causing genes. Subsequently, the pathogenic mutation was validated by Sanger sequencing. Results: We identified 3 brothers, born of consanguineous Chinese parents. These patients were thought to carry autosomal recessive genes. The age of the onset ranged from 8 to 10 years old. All of the patients exhibited a chronic course, then got worse progressively. Parkinsonism was the first symptom. Other clinical features included cognitive decline, ataxia, gait abnormality, dysarthria and spastic paraplegia. All cases showed hypo-intensity in bilateral substantia nigra and globus pallidus on T(2)WI, FLAIR and SWI of MRI. However, the eye-of-the-tiger sign , which was commonly found in pantothenate kinase-associated neurodegeneration (PKAN), was absent. Further findings included cerebellar atrophy (all 3 patients) and the atrophy of temporal lobe (only one brother of the proband). The homozygous mutation c.52G>T (p.Asp18Tyr) was found through WES and Sanger sequencing. The proband s mother was heterozygous. This novel mutation was not reported in mutation database. Consequently, the pathogenic mutation in C19ORF12 gene (exon2, c.2327C>T, p.P776L) was identified from the patients according to the American College of Medical Genetics and Genomics (ACMG) guideline. The final diagnosis of the family was MPAN. Conclusions: We successfully identify a novel p.Asp18Tyr mutation in a family with MPAN. Our finding enriches the known MPAN mutation types and provides evidence for further research.