Mild Isolated Hyperthyrotropinemia Variants Database

Name: Mild Isolated Hyperthyrotropinemia Variants Database
License: https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Keywords: CONGENITAL-HYPOTHYROIDISM

Datos de investigación

Mild Isolated Hyperthyrotropinemia Variants Database

Autores: Tellechea, Mariana Lorena Icon

; Ricci, Valentina; Masnata, María Eugenia; Villanueva Gonzalez, María Denisse

Colaboradores: Chiesa, Ana Elena Icon

Publicador: Consejo Nacional de Investigaciones Científicas y Técnicas

Fecha de depósito: 20/02/2025

Fecha de recolección: 08/01/2025-05/02/2025

Clasificación temática:

Endocrinología y Metabolismo

Resumen

This Systematic Review was conducted in the context of the following project: "Variation Spectra in Mild Isolated Hyperthyrotropinemia: Pilot Cohort and Systematic Review". The purpose was to provide further evidence for the elucidation of the genetic etiology of Mild Hyperthyrotropinemia and to expand the phenotypic and variant spectrum of Congenital Hypothyroidism. We performed a systematic review and reclassification of the disease-causing potential of gene variants using the recommendations of the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP).

Métodos

Information source and search strategy The literature search was done on studies up to 8 Jan 2025 on PubMed database from the National Library of Medicine using the following keywords and terms: (congenital OR neonatal OR newborn OR child OR children OR infant OR toddler) AND ("subclinical hypothyroidism" OR "compensated hypothyroidism" OR hyperthyrotropinemia OR hyperthyreotropinemia OR hyperthyrotrophinaemia OR hyperthyrotropinaemia OR "resistance to thyrotropin" OR "resistance to TSH" OR "TSH resistance" OR "thyrotropin resistance" OR (mild AND "congenital hypothyroidism")) AND (sequencing OR mutation OR variant). Eligibility criteria Eligible studies were limited to those published in English. Articles were screened using the following inclusion criteria: 1) include cases identified by authors as mild HTT or SCH and/or the biochemical phenotype (moderately elevated serum TSH levels with a normal T4 and/or FT4 level for age) can be inferred, preferably with data on TSH and FT4 levels, and 2) the HTT has been diagnosed during the neonatal period (3 months) or childhood (18 years). The TSH cut-off value for inclusion was set arbitrarily at 22 µU/ml considering a variability of 10%. Subjects with goiter or mild hypoplasia were included if they met the inclusion criteria. Cases presenting with T4 and/or FT4 in the normal range with a higher level of TSH (>22 µU/ml) referred to as mild CH, compensated hypothyroidism, or mild-severe TSH resistance were excluded. Patients with positive antithyroid antibodies or TSH levels ? 22 µU/ml at any time, e.g. after L-T4 discontinuation, were also excluded. Patients having evidence of severe thyroid dysgenesis (i.e., thyroid aplasia, ectopia, or hypoplasia) were excluded. Excluded were also studies reporting synonymous single nucleotide variants (SNVs), common sequence variants (“genetic polymorphisms”), or variants classified as benign or likely benign by authors. Finally, we excluded review articles and studies reporting only in vitro experiments. The review protocol can be accessed on request. Selection process and Data extraction VR and MT reviewed titles and abstracts of all records to identify those that would be included in the full-text review. When there was disagreement, a consensus discussion also included MM. Full text and supplementary data were assessed to select studies. Data collection was performed independently by VR and MLT, with any disagreements regarding the inclusion of citations being referred to MM for mediation. No attempts were made to contact the authors of the original articles for information; however, previously published data was occasionally extracted from citations when available. Information was collected using a standardized data collection form from the main manuscript and supplementary material. For family studies with different cases meeting eligibility criteria, data regarding one family member who meets the inclusion criteria, usually the index case, was included. In large families, we extracted one index case per family. Information was extracted from the published studies, along with the article's article ID according to PubMed (PMID) and patient ID. Demographic features (age and gender), biochemical parameters, and radiological findings were recorded. As regards genetic data, we collected the targeted genes and the diagnostic strategy (Sanger sequencing, NGS), gene name, gene variant (variant coding DNA nucleotide change with amino acid change), zygosity (homozygous, heterozygous, hemizygous). Data not available was registered as such. Genomic information of presumably pathogenic or causative variants was extracted from the published studies (raw sequence variant information was recorded as given by the authors). Variant reclassification The list of variants was assembled in an Excel file and mapped onto the human reference genome GRCh37/hg19. Variants with insufficient data for remapping were removed due to uncertainty. The pathogenic potential of the variants was systematically reevaluated with Franklin by Genoox (https://franklin.genoox.com/: Last Accessed January 2025).

Palabras clave: CONGENITAL-HYPOTHYROIDISM, THYROTROPHIN, SEQUENCE-VARIANTS, HYPERTHYROTROPINEMIA

Previsualización destacada

Identificador del recurso

URI: http://hdl.handle.net/11336/254971

Colecciones

Datos de Investigación(CEDIE)
Datos de Investigación de CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"

Citación

Tellechea, Mariana Lorena; Ricci, Valentina; Masnata, María Eugenia; Villanueva Gonzalez, María Denisse; (2025): Mild Isolated Hyperthyrotropinemia Variants Database. Consejo Nacional de Investigaciones Científicas y Técnicas. (dataset). http://hdl.handle.net/11336/254971

Condiciones de uso

Las buenas prácticas científicas esperan que se otorgue el crédito adecuado mediante una citación. Utilice un formato de citación y aplique estas normas de reutilización.

Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)