AI Article Synopsis
- This study investigates the genetic causes of short stature (SS) in a unique group of children from consanguineous families in Sulaimani, Iraq, aiming to enhance understanding of SS genetics and inspire future genetic testing methods for similar populations.
- Out of 64 eligible children with SS, genetic testing revealed a cause in 31 participants (61%), pinpointing pathogenic variants in various genes linked to growth regulation and other biological processes.
- The findings suggest that a customized genetic testing approach is necessary to improve diagnosis rates in SS cases within consanguineous groups, as existing gene panels only identify causes in a limited percentage of cases.
Article Abstract
Introduction: Genetic testing in consanguineous families advances the general comprehension of pathophysiological pathways. However, short stature (SS) genetics remain unexplored in a defined consanguineous cohort. This study examines a unique paediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic testing algorithm for similar populations.
Methods: Among 280 SS referrals 2018-2020, 64 children met inclusion criteria (from consanguineous families; height ≤-2.25 SD), 51 provided informed consent (30 females; 31 syndromic SS) and underwent investigation, primarily via exome sequencing. Prioritized variants were evaluated by ACMG standards. A comparative analysis was conducted by juxtaposing our findings against published gene panels for SS.
Results: A genetic cause of SS was elucidated in 31/51 (61%) participants. Pathogenic variants were found in genes involved in the GH-IGF-1 axis (GHR, SOX3), thyroid axis (TSHR), growth plate (CTSK, COL1A2, COL10A1, DYM, FN1, LTBP3, MMP13, NPR2, SHOX), signal transduction (PTPN11), DNA/RNA replication (DNAJC21, GZF1, LIG4), cytoskeletal structure (CCDC8, FLNA, PCNT), transmembrane transport (SLC34A3, SLC7A7), enzyme coding (CYP27B1, GALNS, GNPTG) and ciliogenesis (CFAP410). Two additional participants had Silver-Russell syndrome and one del22q.11.21. Syndromic SS was predictive in identifying a monogenic condition. Using a gene panel would yield positive results in only 10-33% of cases.
Conclusion: A tailored testing strategy is essential to increase diagnostic yield in children with SS from consanguineous populations.
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| http://dx.doi.org/10.1016/j.gim.2024.101332 | DOI Listing |
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