Novel Cases of Non-Syndromic Hearing Impairment Caused by Pathogenic Variants in Genes Encoding Mitochondrial Aminoacyl-tRNA Synthetases.

Dysfunction of some mitochondrial aminoacyl-tRNA synthetases (encoded by the , , and genes) results in a great variety of phenotypes ranging from non-syndromic hearing impairment (NSHI) to very complex syndromes, with a predominance of neurological signs. The diversity of roles that are played by these moonlighting enzymes and the fact that most pathogenic variants are missense and affect different domains of these proteins in diverse compound heterozygous combinations make it difficult to establish genotype-phenotype correlations. We used a targeted gene-sequencing panel to investigate the presence of pathogenic variants in those four genes in cohorts of 175 Spanish and 18 Colombian familial cases with non-DFNB1 autosomal recessive NSHI.

Clinical and Genetic Characterization of RDH12-Retinal Dystrophy in a South American Cohort.

Purpose: To characterize the largest cohort of individuals with retinol dehydrogenase 12 (RDH12)-retinal dystrophy to date, and the first one from South America.

Design: Retrospective multicenter international study.

Subjects: Seventy-eight patients (66 families) with an inherited retinal dystrophy and biallelic variants in RDH12.

Epigenetic mechanisms and host factors impact ACE2 gene expression: Implications in COVID-19 susceptibility.

Background: The ACE2 protein acts as a gateway for SARS-CoV-2 in the host cell, playing an essential role in susceptibility to infection by this virus. Genetics and epigenetic mechanisms related to the ACE2 gene are associated with changes in its expression and, therefore, linked to increased susceptibility to infection. Although some variables such as sex, age, and obesity have been described as risk factors for COVID-19, the molecular causes involved in the disease susceptibility are still unknown.

Phenotypic characterization of retinitis pigmentosa associated with deafness.

Introduction: There are several syndromes that associate retinitis pigmentosa with deafness or hearing loss. The most frequent is Usher syndrome, a genetic disorder of autosomal recessive inheritance, which, in some cases, is accompanied by vestibular dysfunction. However, there are cases of families that despite having retinitis pigmentosa associated with deafness, cannot be classified as Usher or other syndromes due to additional findings.

Diagnostic definition of malattia leventinese in a family from Colombia.

The malattia leventinese is an autosomal dominant inherited disease whose symptoms appear between the second and fourth decades of life. It is characterized by the appearance of drusen located between the retinal pigment epithelium and the Bruch membrane. It is usually associated with low vision and may progress to blindness.

Genetic association with intravitreal ranibizumab response for neovascular age-related macular degeneration in Hispanic population.

Background/purpose: Age-related macular degeneration (AMD) is the leading cause of visual impairment in patients over 55 years. Currently, the most common therapies for neovascular AMD (nAMD) are intravitreal antiangiogenics. Studies suggest that genetic factors influence on antiangiogenics therapy outcomes.

Detection of hearing loss in newborns: Definition of a screening strategy in Bogotá, Colombia.

Objective: To describe the results from the hearing screening protocol adopted in a Hospital in Colombia emphasizing the importance of performing screening on an outpatient basis, when the newborn is more than 24 h old.

Methods: A prospective study at Hospital Universitario San Ignacio in Bogota, Colombia was carried out, from May 1st, 2016 to Nov 30, 2017, the study sample included 2.088 newborns examined using transient otoacoustic emissions.

Mutational analysis of the LDLR gene in a cohort of Colombian families with familial hypercholesterolemia.

Background And Aims: Familial hypercholesterolemia (FH) is characterized by elevated serum cholesterol levels due to high low-density lipoprotein (LDL) cholesterol levels. FH is an autosomal dominant genetic disorder and one of the most common dominant hereditary diseases in the world. However, the frequency of mutations in Colombia is unknown.

[Phenotypic and molecular characterization of a Colombian family with phenylketonuria].

Phenylketonuria is a metabolic disorder characterized by severe neurological involvement and behavioral disorder, whose early diagnosis enables an effective treatment to avoid disease sequelae, thus changing the prognosis. Objective: To characterize a family with phenylketonuria in Colombia at clinical, biochemical and molecular levels. Materials and methods: The population consisted of seven individuals of a consanguineous family with four children with suggestive symptoms of phenylketonuria.

Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants.

Ethnic-specific differences in minor allele frequency impact variant categorization for genetic screening of nonsyndromic hearing loss (NSHL) and other genetic disorders. We sought to evaluate all previously reported pathogenic NSHL variants in the context of a large number of controls from ethnically distinct populations sequenced with orthogonal massively parallel sequencing methods. We used HGMD, ClinVar, and dbSNP to generate a comprehensive list of reported pathogenic NSHL variants and re-evaluated these variants in the context of 8,595 individuals from 12 populations and 6 ethnically distinct major human evolutionary phylogenetic groups from three sources (Exome Variant Server, 1000 Genomes project, and a control set of individuals created for this study, the OtoDB).

Transient evoked oto-acoustic emission screening in newborns in Bogotá, Colombia: a retrospective study.

Objective: The aim of this study was to investigate the characteristics and performance of transient evoked oto-acoustic emission (TEOAE) hearing screening in newborns in Colombia, and analyze all possible variables and factors affecting the results.

Materials And Methods: An observational, descriptive and retrospective study with bivariate analysis was performed. The study population consisted of 56,822 newborns evaluated at the private institution, PREGEN.

The importance of fundus eye testing in rubella-induced deafness.

Objective: The purpose of this study was to establish a new approach to improve detection of deafness due to rubella.

Methods: Colombian institutes for the deaf were visited by a medical team to perform in all enrolled individuals an ophthalmological examination with emphasis in fundus eye by a retina specialist. In cases where ocular alterations compatible with CRS were found, a medical interview by a clinical geneticist analyzing pre-and postnatal history and a thorough medical examination was done.

[Mutational frequencies in usherin(USH2A gene) in 26 Colombian individuals with Usher syndrome type II].

Introduction: Usher syndrome is a disorder characterized by progressive retinitis pigmentosa, prelingual sensory hearing loss and vestibular dysfunction. It is the most frequent cause of deaf-blindness in humans. Three clinical types and twelve genetic subtypes have been characterized.

Allele-specific impairment of GJB2 expression by GJB6 deletion del(GJB6-D13S1854).

Mutations in the GJB2 gene, which encodes connexin 26, are a frequent cause of congenital non-syndromic sensorineural hearing loss. Two large deletions, del(GJB6-D13S1830) and del(GJB6-D13S1854), which truncate GJB6 (connexin 30), cause hearing loss in individuals homozygous, or compound heterozygous for these deletions or one such deletion and a mutation in GJB2. Recently, we have demonstrated that the del(GJB6-D13S1830) deletion contributes to hearing loss due to an allele-specific lack of GJB2 mRNA expression and not as a result of digenic inheritance, as was postulated earlier.

A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy.

Autosomal recessive nonsyndromic hearing impairment (NSHI) is a heterogeneous condition, for which 53 genetic loci have been reported, and 29 genes have been identified to date. One of these, OTOF, encodes otoferlin, a membrane-anchored calcium-binding protein that plays a role in the exocytosis of synaptic vesicles at the auditory inner hair cell ribbon synapse. We have investigated the prevalence and spectrum of deafness-causing mutations in the OTOF gene.

Screening program for Waardenburg syndrome in Colombia: clinical definition and phenotypic variability.

A screening program to detect Waardenburg syndrome (WS) conducted between 2002 and 2005, among 1,763 deaf individuals throughout Columbia identified 95 affected individuals belonging to 95 families, giving a frequency of 5.38% of WS among the institutionalized deaf population. We confirmed the clinical diagnosis of WS in the 95 propositi and, through the family evaluation, we also identified 45 non-institutionalized affected relatives.

Mitochondrial DNA studies show asymmetrical Amerindian admixture in Afro-Colombian and Mestizo populations.

The origin of the African populations that arrived on the Colombian coasts at the time of the Spanish conquest and their subsequent settlement throughout the country and interaction with Amerindian and Spanish populations are features that can be analyzed through the study of mitochondrial DNA (mtDNA) markers. For this purpose, the present study investigates the admixture between these populations by analyzing the markers defining the main (A, B, C, D) and minor (X) founder haplogroups in Native Americans, the principal African haplogroup (L), and additional generic markers present in Caucasian (I, J, K, H, T, U, V, W) and minor African lineages (L3). As part of an interdisciplinary research program (the Expedición Humana, furthered by the Universidad Javeriana and directed by J.

Possible migration routes into South America deduced from mitochondrial DNA studies in Colombian Amerindian populations.

Mitochondrial DNA haplotype studies have been useful in unraveling the origins of Native Americans. Such studies are based on restriction site and intergenic deletion/insertion polymorphisms, which define four main haplotype groups common to Asian and American populations. Several studies have characterized these lineages in North, Central, and South American Amerindian, as well as Na Dene and Aleutian populations.