Biallelic loss-of-function variants in WDR11 are associated with microcephaly and intellectual disability

Natja Haag, Ene Choo Tan, Matthias Begemann, Lars Buschmann, Florian Kraft, Petra Holschbach, Angeline H.M. Lai, Maggie Brett, Ganeshwaran H. Mochida, Stephanie DiTroia, Lynn Pais, Jennifer E. Neil, Muna Al-Saffar, Laila Bastaki, Christopher A. Walsh, Ingo Kurth, Cordula Knopp

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1663-1668
Number of pages6
JournalEuropean Journal of Human Genetics
Issue number11
Publication statusPublished - Nov 2021

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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