ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2020) 17 1.4 | DOI: 10.1530/ey.17.1.4

Update on the Genetics of Hypopituitarism

1.4. Loss-of-function variants in TBC1D32 underlie syndromic hypopituitarism

Hietamäki J, Gregory LC, Ayoub S, Iivonen AP, Vaaralahti K, Liu X, Brandstack N, Buckton AJ, Laine T, Känsäkoski J, Hero M, Miettinen PJ, Varjosalo M, Wakeling E, Dattani MT & Raivio T


To read the full abstract: J Clin Endocrinol Metab. 2020 Feb 15. pii: dgaa078. doi: 10.1210/clinem/dgaa078. PMID: 32060556.

Just another gene implicated in hypopituitarism? Yes, but it is a newish cilopathy gene in the hedgehog pathway. Hedgehog family of polypeptides (Sonic (Shh), Indian (Ihh) and desert (Dhh) hedgehog) are signaling molecules that are needed for many cellular events and play a role in both embryogenesis and adult physiology. Mutations in these genes result in subsequent deficiency of the downstream signaling pathways and in defects in brain, limb, and vertebral development, and, more specifically, they have been implicated in e.g. holoprosencephaly and Simpson-Golami-Behmel syndrome and in cilopathies. The mouse homologue of TBC1D32, Bromi is needed for the appropriate activation of Shh signaling and as TBC1D32 is part of the non-motile cilium, the loss-of function of TBC1D32 phenotype of hypopituitarism and craniofacial dysmorphism is a cilopathy. A new review of hedgehog signalling and genetic disorders was recently published (Sasai N et al., Front Genet. 2019 Nov 8;10:1103. doi: 10.3389/fgene.2019.01103. eCollection 2019).

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