Pituitary morphovolumetric changes in Alström syndrome

Loss of function BMP4 mutation supports the implication of the BMP/TGF‐β pathway in the etiology of combined pituitary hormone deficiency

“…In the present case we identified four additional transmitted, potentially relevant variants in the proband, in four genes expressed in the pituitary gland and hypothalamus (Uhlén et al, ), implicated in three different signaling pathways regulating embryonic pituitary development (Table ). Two rare missense variants in SMAD4 and E2F4 , also involved, as BMP4 , in the BMP/TGF‐β signaling pathway (Chen, Kang, Siegel, & Massagué, ); a novel frameshift variant in ALMS1 , which encodes a transcription factor regulating NOTCH signaling (Leitch, Lodh, Prieto‐Echagüe, Badano, & Zaghloul, ), implicated in the etiology of Alström syndrome (MIM #203800) and associated endocrinopathies (Citton et al, ; Han et al, ), and a rare missense variant in TSHZ1 , which is implicated in the Prokineticin signaling pathway regulating PROKR2 expression and olfactory bulbs' development (Ragancokova et al, ), and thereby, linked with the etiology of congenital hypogonadotropic hypogonadism. Interestingly, SMAD4 is an important intracellular effector of the BMP/TGF‐β pathway, which in the cell nucleus interacts with E2F4 forming a transcriptional regulatory complex (Chen et al, ).…”