Detection of del/dup inside SHOX/PAR1 region in children and young adults with idiopathic short stature

Stritar, Jera (author), Stavber, Lana (author), Ficko, Maja (author), Kotnik, Primož (author), Battelino, Tadej (author), Trebušak Podkrajšek, Katarina (author), Hovnik, Tinka (author)

Short stature is a common growth disorder defined as a body height two standard deviations (SD) or more below the mean for a given age, gender, and population. A large part of the cases remains unexplained and is referred to as having idiopathic short stature (ISS). One of the leading genetic causes of short stature is variants of short stature homeobox-containing gene (SHOX) and is considered to be responsible for 2–15% of ISS. We aimed to analyse the regulatory and coding region of SHOX in Slovenian children and young adults with ISS and to investigate the pathogenicity of detected variants. Our cohort included 75 children and young adults with ISS. Multiplex ligation-dependent probe amplification (MLPA) was performed in all participants for the detection of larger copy number variations (CNVs). Sanger sequencing was undertaken for the detection of point variants, small deletions, and insertions. A total of one deletion and two duplications were discovered using the MLPA technique. Only one of these four variants was identified as disease-causing and occurred in one individual, which represents 1.3% of the cohort. With Sanger sequencing, two variants were discovered, but none of them appeared to have a pathogenic effect on height. According to the results, in the Slovenian population of children and young adults with ISS, SHOX deficiency is less frequent than expected considering existing data from other populations.

• Language: English
• Keywords: idiopathic short stature, Sanger sequencing, children and young adults, height, short stature, SHOX, MLPA
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 7 str.
• Numbering: Vol. 12, iss. 10, art. 1546
• PID: 20.500.12556/RUL-136293
• UDC: 616.4
• ISSN on article: 2073-4425
• DOI: 10.3390/genes12101546
• COBISS.SI-ID: 79106563
• Publication date in RUL: 22.04.2022

Record is a part of a journal

• Title: Genes
• Shortened title: Genes
• Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
• ISSN: 2073-4425
• COBISS.SI-ID: 523100185

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.10.2021

Secondary language

• Language: Slovenian
• Keywords: idiopatska nizka rast, Sangerjevo zaporedje, otroci in mladostniki

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0343
• Name: Etiologija, zgodnje odkrivanje in zdravljenje bolezni pri otrocih in mladostnikih

• Funder: Other - Other funder or multiple funders
• Funding programme: Tertiary research
• Project number: TP 20170122