{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:15:44Z","timestamp":1760235344281,"version":"build-2065373602"},"reference-count":127,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica, Argentina.","award":["Pr\u00e9stamo BID PICT 2018-00579"],"award-info":[{"award-number":["Pr\u00e9stamo BID PICT 2018-00579"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Heritability accounts for over 80% of adult human height, indicating that genetic variability is the main determinant of stature. The rapid technological development of Next-Generation Sequencing (NGS), particularly Whole Exome Sequencing (WES), has resulted in the characterization of several genetic conditions affecting growth and development. The greatest challenge of NGS remains the high number of candidate variants identified. In silico bioinformatic tools represent the first approach for classifying these variants. However, solving the complicated problem of variant interpretation requires the use of experimental approaches such as in vitro and, when needed, in vivo functional assays. In this review, we will discuss a rational approach to apply to the gene variants identified in children with growth and developmental defects including: (i) bioinformatic tools; (ii) in silico modeling tools; (iii) in vitro functional assays; and (iv) the development of in vivo models. While bioinformatic tools are useful for a preliminary selection of potentially pathogenic variants, in vitro\u2014and sometimes also in vivo\u2014functional assays are further required to unequivocally determine the pathogenicity of a novel genetic variant. This long, time-consuming, and expensive process is the only scientifically proven method to determine causality between a genetic variant and a human genetic disease.<\/jats:p>","DOI":"10.3390\/cells10082063","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T10:54:41Z","timestamp":1628765681000},"page":"2063","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Applying Bioinformatic Platforms, In Vitro, and In Vivo Functional Assays in the Characterization of Genetic Variants in the GH\/IGF Pathway Affecting Growth and Development"],"prefix":"10.3390","volume":"10","author":[{"given":"Sabina","family":"Domen\u00e9","sequence":"first","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr C\u00e9sar Bergad\u00e1\u2019, (CEDIE) CONICET, FEI, Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez), Buenos Aires C1425EFD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula A.","family":"Scaglia","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr C\u00e9sar Bergad\u00e1\u2019, (CEDIE) CONICET, FEI, Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez), Buenos Aires C1425EFD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana L.","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr C\u00e9sar Bergad\u00e1\u2019, (CEDIE) CONICET, FEI, Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez), Buenos Aires C1425EFD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Horacio M.","family":"Domen\u00e9","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr C\u00e9sar Bergad\u00e1\u2019, (CEDIE) CONICET, FEI, Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez), Buenos Aires C1425EFD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1375\/136905203770326402","article-title":"Heritability of adult body height: A comparative study of twin cohorts in eight countries","volume":"6","author":"Silventoinen","year":"2003","journal-title":"J. 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