High yield of monogenic short stature in children from Kurdistan, Iraq: A genetic testing algorithm for consanguineous families

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 pediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic tes...

Celý popis

Uložené v:
Podrobná bibliografia
Vydané v:Genetics in medicine Ročník 27; číslo 2; s. 101332
Hlavní autori: Amaratunga, Shenali Anne, Tayeb, Tara Hussein, Dusatkova, Petra, Elblova, Lenka, Drabova, Jana, Plachy, Lukas, Pruhova, Stepanka, Lebl, Jan
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 01.02.2025
Predmet:
Adolescent
Algorithms
Body Height - genetics
Child
Child, Preschool
Consanguinity
Dwarfism - diagnosis
Dwarfism - epidemiology
Dwarfism - genetics
Exome Sequencing
Female
Genetic Testing - methods
Humans
Iraq - epidemiology
Male
Pedigree
Iraq
Genetic testing algorithm
Short stature
Consanguinity
Short stature genes
Pediatric endocrinology
ISSN:1530-0366, 1530-0366
On-line prístup:Zistit podrobnosti o prístupe
Tagy: Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
Popis
Shrnutí: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 pediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic testing algorithm for similar populations. Among 280 SS referrals from 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 the American College of Medical Genetics and Genomics standards. A comparative analysis was conducted by juxtaposing our findings against published gene panels for SS. A genetic cause of SS was elucidated in 31 of 51 (61%) participants. Pathogenic variants were found in genes involved in the GH-IGF-1 axis (GHR and SOX3), thyroid axis (TSHR), growth plate (CTSK, COL1A2, COL10A1, DYM, FN1, LTBP3, MMP13, NPR2, and SHOX), signal transduction (PTPN11), DNA/RNA replication (DNAJC21, GZF1, and LIG4), cytoskeletal structure (CCDC8, FLNA, and PCNT), transmembrane transport (SLC34A3 and SLC7A7), enzyme coding (CYP27B1, GALNS, and GNPTG), and ciliogenesis (CFAP410). Two additional participants had Silver-Russell syndrome and 1 had del22q.11.21. Syndromic SS was predictive in identifying a monogenic condition. Using a gene panel would yield positive results in only 10% to 33% of cases. A tailored testing strategy is essential to increase diagnostic yield in children with SS from consanguineous populations.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1530-0366
1530-0366
DOI:10.1016/j.gim.2024.101332