Patients who suffer from congenital hypopituitarism display a wide spectrum of phenotypes including pituitary hormone deficiencies and, in some cases, additional extrapituitary manifestations depending on the causative gene. A group of genes underlying hypopituitarism has been identified, yet several of them remain unknown. Here, we identified compound heterozygous variants in the TBC1D32 gene, c.1165_1166dupGT, p.(Gln390Phefs*32) and c.2151delA, p.(Lys717Asnfs*29) in two affected siblings with congenital hypopituitarism by analyzing whole-genome seguencing (WGS) data and confirming the findings by Sanger sequencing. The c.1165_1166insGT p.(Gln390Phefs*32) (rs546631812) variant had a frequency of 0.009348 in the Finnish population and was carried by the father and healthy brother. The c.2151delA p.(Lys717Asnfs*29) variant was absent in databases and was carried by the mother. TBC1D32 has previously been implicated in Sonic hedgehog (Shh) signaling, which is crucial in the development of craniofacial features and causes ciliopathies when disrupted. Mutations in TBC1D32 have previously been found in an oro-facio-digital syndrome type IX patient who displayed an overlapping phenotype with those of our patients. Our results suggest that TBC1D32 mutations should be considered as potential causes of ciliopathy-like syndromic hypopituitarism.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology