AUTHOR=Kazakova Ekaterina , Téllez-Martínez José Alberto , Flores-Lagunes Leonardo , Sosa-Ortiz Ana Luisa , Carillo-Sánchez Karol , Molina-Garay Carolina , González-Domínguez Carlos Alberto , Jimenez-Olivares Marco , Fernandez-Valverde Francisca , Vargas-Cañas Edwin Steven , Vázquez-Memije Martha Elisa , Garcia-Latorre Ethel Awilda , Martínez-Duncker Iván , Alaez-Verson Carmen 

TITLE=Uterus infantilis: a novel phenotype associated with AARS2 new genetic variants. A case report

JOURNAL=Frontiers in Neurology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.878446

DOI=10.3389/fneur.2023.878446

ISSN=1664-2295

ABSTRACT=<sec><title>Objectives</title><p>To report the first Mexican case with two novel <italic>AARS2</italic> mutations causing primary ovarian failure, uterus <italic>infantilis</italic>, and early-onset dementia secondary to leukoencephalopathy.</p></sec><sec><title>Methods</title><p>Detailed clinical, clinimetric, neuroimaging features, muscle biopsy with biochemical assays of the main oxidative phosphorylation complexes activities, and molecular studies were performed on samples from a Mexican female.</p></sec><sec><title>Results</title><p>We present a 41-year-old female patient with learning difficulties since childhood and primary amenorrhea who developed severe cognitive, motor, and behavioral impairment in early adulthood. Neuroimaging studies revealed frontal leukoencephalopathy with hypometabolism at the fronto-cerebellar cortex and caudate nucleus. Uterus <italic>infantilis</italic> was detected on ultrasound study. Clinical exome sequencing identified two novel variants, NM_020745:c.2864G&gt;A (p.W955<sup>*</sup>) and NM_020745:c.1036C&gt;A (p.P346T, p.P346Wfs<sup>*</sup>18), in <italic>AARS2</italic>. Histopathological and biochemical studies on muscle biopsy revealed mitochondrial disorder with cytochrome C oxidase (COX) deficiency.</p></sec><sec><title>Conclusions</title><p>Several adult-onset cases of leukoencephalopathy and ovarian failure associated with <italic>AARS2</italic> variants have been reported. To our best knowledge, none of them showed uterus <italic>infantilis</italic>. Here we enlarge the genetic and phenotypic spectrum of <italic>AARS2</italic>-related dementia with leukoencephalopathy and ovarian failure and contribute with detailed clinical, clinometric, neuroimaging, and molecular studies to disease and novel molecular variants characterization.</p></sec>