Etiology of combined pituitary hormone deficiency: GNAO1 as a novel candidate gene

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F24%3A10482440" target="_blank" >RIV/00216208:11130/24:10482440 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064203:_____/24:10482440

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rTqHD3zcie" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rTqHD3zcie</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1530/EC-24-0217" target="_blank" >10.1530/EC-24-0217</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Etiology of combined pituitary hormone deficiency: GNAO1 as a novel candidate gene

Popis výsledku v původním jazyce

Because causes of combined pituitary hormone deficiency (CPHD) are complex, the etiology of congenital CPHD remains unknown in most cases. The aim of the study was to identify the genetic etiology of CPHD in a well-defined single-center cohort. In total, 34 children (12 girls) with congenital CPHD (growth hormone (GH) deficiency and impaired secretion of at least one other pituitary hormone) treated with GH in our center were enrolled to the study. Their median age was 11.2 years, pre-treatment height -3.2 SD, and maximal stimulated GH 1.4 ug/L. Of them, 30 had central adrenal insufficiency, 27 central hypothyroidism, 10 hypogonadotropic hypogonadism, 3 central diabetes insipidus. Twenty-six children had a midline defect on MRI. Children with a clinical suspicion on specific genetic disorder underwent genetic examination of the gene(s) of interest via Sanger sequencing or array comparative genomic hybridization. Children without detected causal variant after the first-tier testing or with no suspicion of specific genetic disorder were subsequently examined using next-generation sequencing growth panel. Variants were evaluated by the American College of Medical Genetics standards. Genetic etiology was confirmed in 7/34 (21%) children. Chromosomal aberrations were found in one child (14q microdeletion involving OTX2 gene). The remaining 6 children had causative genetic variants in GLI2, PROP1, POU1F1, TBX3, PMM2, and GNAO1 genes, respectively. We elucidated cause of CPHD in a fifth of patients. Our study supports the PMM2 gene as a candidate gene for CPHD and suggests pathogenic variants in the GNAO1 gene as a potential novel genetic cause of CPHD..

Název v anglickém jazyce

Etiology of combined pituitary hormone deficiency: GNAO1 as a novel candidate gene

Popis výsledku anglicky

Because causes of combined pituitary hormone deficiency (CPHD) are complex, the etiology of congenital CPHD remains unknown in most cases. The aim of the study was to identify the genetic etiology of CPHD in a well-defined single-center cohort. In total, 34 children (12 girls) with congenital CPHD (growth hormone (GH) deficiency and impaired secretion of at least one other pituitary hormone) treated with GH in our center were enrolled to the study. Their median age was 11.2 years, pre-treatment height -3.2 SD, and maximal stimulated GH 1.4 ug/L. Of them, 30 had central adrenal insufficiency, 27 central hypothyroidism, 10 hypogonadotropic hypogonadism, 3 central diabetes insipidus. Twenty-six children had a midline defect on MRI. Children with a clinical suspicion on specific genetic disorder underwent genetic examination of the gene(s) of interest via Sanger sequencing or array comparative genomic hybridization. Children without detected causal variant after the first-tier testing or with no suspicion of specific genetic disorder were subsequently examined using next-generation sequencing growth panel. Variants were evaluated by the American College of Medical Genetics standards. Genetic etiology was confirmed in 7/34 (21%) children. Chromosomal aberrations were found in one child (14q microdeletion involving OTX2 gene). The remaining 6 children had causative genetic variants in GLI2, PROP1, POU1F1, TBX3, PMM2, and GNAO1 genes, respectively. We elucidated cause of CPHD in a fifth of patients. Our study supports the PMM2 gene as a candidate gene for CPHD and suggests pathogenic variants in the GNAO1 gene as a potential novel genetic cause of CPHD..

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30209 - Paediatrics

Projekt

<a href="/cs/project/NU22J-07-00014" target="_blank" >NU22J-07-00014: Objasnění etiopatogeneze poruchy růstu u dětí s klinickou diagnózou deficitu růstového hormonu pomocí moderních genetických metod jako cesta k optimalizaci diagnostiky a léčby</a><br>

Návaznosti

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

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Endocrine Connections

ISSN

2049-3614

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

e240217

Kód UT WoS článku

001382057600007

EID výsledku v databázi Scopus

2-s2.0-85203189216