SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis.
Endocrine
; 84(2): 345-349, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38400880
ABSTRACT
PURPOSE:
Disorders/differences of sex development (DSD) result from variants in many different human genes but, frequently, have no detectable molecular cause.METHODS:
Detailed clinical and genetic phenotyping was conducted on a family with three children. A Sec31a animal model and functional studies were used to investigate the significance of the findings.RESULTS:
By trio whole-exome DNA sequencing we detected a heterozygous de novo nonsense SEC31A variant, in three children of healthy non-consanguineous parents. The children had different combinations of disorders that included complete gonadal dysgenesis and multiple pituitary hormone deficiency. SEC31A encodes a component of the COPII coat protein complex, necessary for intracellular anterograde vesicle-mediated transport between the endoplasmic reticulum (ER) and Golgi. CRISPR-Cas9 targeted knockout of the orthologous Sec31a gene region resulted in early embryonic lethality in homozygous mice. mRNA expression of ER-stress genes ATF4 and CHOP was increased in the children, suggesting defective protein transport. The pLI score of the gene, from gnomAD data, is 0.02.CONCLUSIONS:
SEC31A might underlie a previously unrecognised clinical syndrome comprising gonadal dysgenesis, multiple pituitary hormone deficiencies, dysmorphic features and developmental delay. However, a variant that remains undetected, in a different gene, may alternatively be causal in this family.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Disgenesia Gonadal
/
Hipopituitarismo
Limite:
Animals
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Endocrine
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Reino Unido