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Analysis of children with familial short stature: who should be indicated for genetic testing?

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F23%3A10466490" target="_blank" >RIV/00216208:11130/23:10466490 - isvavai.cz</a>

  • Alternative codes found

    RIV/00064203:_____/23:10466490

  • Result on the web

    <a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=vQ-FR9HVSX" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=vQ-FR9HVSX</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1530/EC-23-0238" target="_blank" >10.1530/EC-23-0238</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Analysis of children with familial short stature: who should be indicated for genetic testing?

  • Original language description

    Familial short stature (FSS) describes vertically transmitted growth disorders. Traditionally, polygenic inheritance is presumed, but monogenic inheritance seems to occur more frequently than expected. Clinical predictors of monogenic FSS have not been elucidated. The aim of the study was to identify the monogenic etiology and its clinical predictors in FSS children. Of 747 patients treated with growth hormone (GH) in our center, 95 with FSS met the inclusion criteria (pretreatment height &lt;=-2 SD in child and his/her shorter parent, excluded secondary short stature, excluded Turner/Prader-Willi syndrome). Genetic etiology was known in 11/95 children before the study, remaining 84 were examined by next-generation sequencing. The results were evaluated by ACMG guidelines. Nonparametric tests evaluated differences between monogenic and non-monogenic FSS, an ROC curve estimated quantitative cutoffs for the predictors. Monogenic FSS was confirmed in 36/95 (38%) children. Of these, 29 (81%) carried a causative genetic variant affecting the growth plate, four (11%) a variant affecting GH-IGF1 axis, and three (8%) a variant in miscellaneous genes. Lower shorter parent&apos;s height (p=0.015) and less delayed bone age (BA) before GH treatment (p=0.026) predicted monogenic FSS. In children with BA delayed less than 0.4 years and with shorter parent heights &lt;-2.4 SD, monogenic FSS was revealed in 13/16 (81%) cases. To conclude, in FSS children treated with GH, a monogenic etiology is frequent, gene variants affecting the growth plate are the most common. Shorter parent&apos;s height and bone age are clinical predictors of monogenic FSS.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30209 - Paediatrics

Result continuities

  • Project

    <a href="/en/project/NV18-07-00283" target="_blank" >NV18-07-00283: Studies of aetiopathogenesis and optimising management in children with intrauterine growth restriction and persistent postnatal growth failure</a><br>

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2023

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Endocrine Connections

  • ISSN

    2049-3614

  • e-ISSN

  • Volume of the periodical

    12

  • Issue of the periodical within the volume

    10

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    8

  • Pages from-to

    e230238

  • UT code for WoS article

    001082008100004

  • EID of the result in the Scopus database

    2-s2.0-85172695913