Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic.

ABSTRACT:

Purpose

Congenital hypopituitarism usually occurs sporadically. In most patients, the etiology remains unknown.

Methods

We studied 13 children with sporadic congenital hypopituitarism. Children with non-endocrine, non-familial idiopathic short stature (NFSS) (n = 19) served as a control group. Exome sequencing was performed in probands and both unaffected parents. A burden testing approach was used to compare the number of candidate variants in the two groups.

Results

First, we assessed the frequency of rare, predicted-pathogenic variants in 42 genes previously reported to be associated with pituitary gland development. The average number of variants per individual was greater in probands with congenital hypopituitarism than those with NFSS (1.1 vs. 0.21, mean

SUBMITTER: Jee YH 

PROVIDER: S-EPMC8386283 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature