Report of a progressive leukoencephalopathy with ovarian failure (LKENP) case with compound heterozygous genotype and a novel variant: AARS2:c.2358_2364+7dup

Abstract

Leukoencephalopathies are a heterogeneous group of diseases in which many acquired and hereditary factors play a role in its etiopathogenesis. In recent years, Alanyl-tRNA synthetase 2 (AARS2), encoded by the nuclear genome, has been identified as the causative gene in a small number of patients. The AARS2 gene is responsible for the “progressive leukoencephalopathy with ovarian failure (LKENP)” phenotype, an extremely rare syndrome characterized by progressive leukoencephalopathy and premature ovarian failure. In this case report; we describe the delayed diagnosis of LKENP by genetic analysis using a large gene panel, in a female who was followed up in different clinics for many years with clinical findings of early ovarian failure, amnesia, depression, young-onset dementia, early ovarian failure and leukoencephalopathy. As a result of genetic analysis of the patient using NGS-based targeted multigene panel testing, disease-related variants in the AARS2 gene were found to be compound heterozygous. These; reported in the literature as NM_020745.4(AARS2):c.1709delG (p.Gly570AlafsTer21) and novel NM_020745.4(AARS2):c.2358_2364+7dupCCAGCAGGTCAGCA variants. When the clinical and radiological findings observed in our case were evaluated together, LKENP was considered in the preliminary diagnosis among all adult-onset leukoencephalopathy types. In this rare hereditary type of leukoencephalopathy, molecular genetic tests was important in elucidating etiopathogenesis.