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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F25%3A10487773" target="_blank" >RIV/00064203:_____/25:10487773 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/25:10487773

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=MqJilmsZBG" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=MqJilmsZBG</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.gim.2024.101332" target="_blank" >10.1016/j.gim.2024.101332</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 &lt;=-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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 &lt;=-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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30209 - Paediatrics

Projekt

<a href="/cs/project/LM2018132" target="_blank" >LM2018132: Národní centrum lékařské genomiky</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Genetics in Medicine

ISSN

1098-3600

e-ISSN

1530-0366

Svazek periodika

27

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

101332

Kód UT WoS článku

001414276100001

EID výsledku v databázi Scopus

2-s2.0-85214089349