Fig. 1: Identification of WSB2 variants in five patients featuring syndromic NDDs. | European Journal of Human Genetics

Fig. 1: Identification of WSB2 variants in five patients featuring syndromic NDDs.

From: Recessive variants in WSB2 encoding a substrate receptor of E3 ubiquitin ligase underlie a neurodevelopmental syndrome

Fig. 1

A Representative schematic of WSB2 gene (NM_018639.5) containing seven WD-repeats and a suppressor of cytokine signaling (SOCS) box in the C-terminus. The WSB2 variants are positioned in WD1, WD2, and SOCS box domain, respectively. B Molecular modeling of WSB2 missense variant (NM_018639.5: c.1121G>A, p.Arg374Gln). As shown in the top panel, the wildtype residue’s (Arg374, red) positively charged side chain interacts with the aromatic rings of Phe398 and Phe404 (shown in blue), helping stabilize this region. In contrast, the side chain of Gln374 (red, bottom panel) forms weaker hydrophobic contacts with these phenylalanine, thereby potentially increasing local flexibility of the SOCS box domain. C Representative magnetic resonance imaging (MRI) of patient 2 with homozygous c.399del p.(Q134Rfs*14) at 12 months of age. (i) Sagittal T1-weighted MRI showing microcephaly, callosal hypogenesis (white arrow), tectal dysplasia (yellow arrow), and severe cerebellar hypoplasia/atrophy (dotted oval). (ii and iii) Axial T1- and T2-weighted MRI show undersulcation and white matter hypomyelination for age. (iv-vi) Coronal T2-weighted with fat suppression show small olfactory bulbs (black arrows), optic nerves (white arrows), and hippocampi (yellow arrows).

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