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Observational Study
. 2025;98(5):532-542.
doi: 10.1159/000539696. Epub 2024 Jun 5.

Genetic Findings in Short Turkish Children Born to Consanguineous Parents

Sjoerd D Joustra, Sjoerd D Joustra  1 , Emregul Isik  2 , Jan M Wit  1 , Gonul Catli  3   4 , Ahmet Anik  5 , Belma Haliloglu  6 , Nurgun Kandemir  7 , Elif Ozsu  8 , Yvonne M C Hendriks  9 , Christiaan de Bruin  1 , Sarina G Kant  10 , Angel Campos-Barros  11   12 , Rachel C Challis  13 , David Parry  13 , Margaret E Harley  13 , Andrew Jackson  13 , Monique Losekoot  9 , Hermine A van Duyvenvoorde  9
Affiliations
Observational Study

Genetic Findings in Short Turkish Children Born to Consanguineous Parents

Sjoerd D Joustra et al. Horm Res Paediatr. 2025.

Abstract

Introduction: The diagnostic yield of genetic analysis in the evaluation of children with short stature depends on associated clinical characteristics, but the additional effect of parental consanguinity has not been well documented.

Methods: This observational case series of 42 short children from 34 consanguineous families was collected by six referral centres of paediatric endocrinology (inclusion criteria: short stature and parental consanguinity). In 18 patients (12 families, group 1), the clinical features suggested a specific genetic defect in the growth hormone (GH) insulin-like growth factor I (IGF-I) axis, and a candidate gene approach was used. In others (group 2), a hypothesis-free approach was chosen (gene panels, microarray analysis, and whole exome sequencing) and further subdivided into 11 patients with severe short stature (height <-3.5 standard deviation score [SDS]) and microcephaly (head circumference <-3.0 SDS) (group 2a), 10 patients with syndromic short stature (group 2b), and 3 patients with nonspecific isolated GH deficiency (group 2c).

Results: In all 12 families from group 1, (likely) pathogenic variants were identified in GHR, IGFALS, GH1, and STAT5B. In 9/12 families from group 2a, variants were detected in PCNT, SMARCAL1, SRCAP, WDR4, and GHSR. In 5/9 families from group 2b, variants were found in TTC37, SCUBE3, NSD2, RABGAP1, and 17p13.3 microdeletions. In group 2c, no genetic cause was found. Homozygous, compound heterozygous, and heterozygous variants were found in 21, 1, and 4 patients, respectively.

Conclusion: Genetic testing in short children from consanguineous parents has a high diagnostic yield, especially in cases of severe GH deficiency or insensitivity, microcephaly, and syndromic short stature.

Keywords: Consanguinity; Copy number variants; Growth hormone; Short stature; Single nucleotide variants.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1.
Fig. 1.
Diagram showing the selection of short patients with consanguineous parents who were investigated and the results.
See this image and copyright information in PMC

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