In:
European Journal of Human Genetics, Springer Science and Business Media LLC, Vol. 29, No. 11 ( 2021-11), p. 1663-1668
Abstract:
Heterozygous missense variants in the WD repeat domain 11 ( WDR11 ) gene are associated with hypogonadotropic hypogonadism in humans. In contrast, knockout of both alleles of Wdr11 in mice results in a more severe phenotype with growth and developmental delay, features of holoprosencephaly, heart defects and reproductive disorders. Similar developmental defects known to be associated with aberrant hedgehog signaling and ciliogenesis have been found in zebrafish after Wdr11 knockdown. We here report biallelic loss-of-function variants in the WDR11 gene in six patients from three independent families with intellectual disability, microcephaly and short stature. The findings suggest that biallelic WDR11 variants in humans result in an overlapping but milder phenotype compared to Wdr11 -deficient animals. However, the observed human phenotype differs significantly from dominantly inherited variants leading to hypogonadotropic hypogonadism, suggesting that recessive WDR11 variants result in a clinically distinct entity.
Type of Medium:
Online Resource
ISSN:
1018-4813
,
1476-5438
DOI:
10.1038/s41431-021-00943-5
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2005160-8
SSG:
12
