Genetic Findings in Short Turkish Children Born to Consanguineous Parents.

Autor:	Joustra SD; Department of Paediatrics, Division of Pediatric Endocrinology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands., Isik E; Department of Paediatrics, Ankara Bilkent City Hospital, Ankara, Turkey., Wit JM; Department of Paediatrics, Division of Pediatric Endocrinology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands., Catli G; Department of Paediatric Endocrinology, Izmir Katip Celebi University Faculty of Medicine, Izmir, Turkey.; Department of Paediatric Endocrinology, Istinye University Faculty of Medicine, Istanbul, Turkey., Anik A; Department of Paediatric Endocrinology, Dokuz Eylul University, Izmir, Turkey., Haliloglu B; Department of Paediatric Endocrinology and Diabetology, Marmara University School of Medicine, Istanbul, Turkey., Kandemir N; Department of Paediatric Endocrinology, Hacettepe University, Faculty of Medicine, Ankara, Turkey., Ozsu E; Department of Paediatric Endocrinology and Diabetes, University of Ankara, Ankara, Turkey., Hendriks YMC; Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands., de Bruin C; Department of Paediatrics, Division of Pediatric Endocrinology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands., Kant SG; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands., Campos-Barros A; Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.; Rare Diseases Biomedical Research Network (CIBERER; U 753), ISCIII, Madrid, Spain., Challis RC; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Parry D; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Harley ME; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Jackson A; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Losekoot M; Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands., van Duyvenvoorde HA; Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
Jazyk:	angličtina
Zdroj:	Hormone research in paediatrics [Horm Res Paediatr] 2024 Jun 05, pp. 1-11. Date of Electronic Publication: 2024 Jun 05.
DOI:	10.1159/000539696
Abstrakt:	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. (© 2024 The Author(s). Published by S. Karger AG, Basel.)
Databáze:	MEDLINE
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