Sagittal Craniosynostosis with Uncommon Anatomical Pathologies in a 56-Year-Old Male Cadaver
Table 1
Selected deleterious (pathologic) genetic variants associated with the current case of sagittal craniosynostosis.
Gene
Protein function
Variant
MAF
ARHGAP21
Rho GTPase Activating Protein 21. Functions as a GTPase-activating protein (GAP) for RHOA and CDC42.
p.Arg492Gly
0.0021
BMP6
Bone morphogenetic protein 6. Teeth development. Cartilage development. Endochondral ossification. Positive regulation of osteoblast differentiation. Positive regulation of bone mineralization. Positive regulation of chondrocyte differentiation.
p.Pro93Ser
0.0001
CEP162
Centrosomal protein of 162 kDa. Required to promote assembly of the transition zone in primary cilia. Acts by specifically recognizing and binding the axonemal microtubule. Required to mediate CEP290 association with microtubules.
p.Arg802Trp
0.0001
p.Arg878Trp
CROCC
Rootletin. Major structural component of the ciliary rootlet, a cytoskeletal-like structure in ciliated cells which originates from the basal body at the proximal end of a cilium and extends proximally toward the cell nucleus (by similarity). Required for the correct positioning of the cilium basal body relative to the cell nucleus, to allow for ciliogenesis.
p.Arg637Trp
0.0001
DNAH11
Dynein heavy chain 11, axonemal. Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP.
p.Pro2006Leu
0.0001
GMIP
GEM-interacting protein. Stimulates, in vitro and in vivo, the GTPase activity of RhoA.
p.Pro532Leu
0.0001
p.Pro535Leu
p.Pro561Leu
INADL
InaD-like protein also known as PATJ. Negative regulator of Wnt signaling. Blocks DFz1 activity in the planar cell polarity pathway (PCP) in cooperation with atypical PKC. Fzd/PCP pathway represents the noncanonical Wnt signaling.
p.Glu1499Lys
0.0099
PIEZO1
Piezo-type mechanosensitive ion channel component 1. Pore-forming subunit of a mechanosensitive nonspecific cation channel. Plays a key role in osteogenesis. Its activation commits mesenchymal stem cells to osteogenic differentiation.
p.Pro2510Leu
0.0042
RNF213
E3 ubiquitin-protein ligase RNF213. Involved in the noncanonical Wnt signaling pathway in vascular development: acts by mediating ubiquitination and degradation of FLNA and NFATC2 downstream of RSPO3, leading to the inhibition of the noncanonical Wnt signaling pathway and promoting vessel regression.
p.Trp4677Leu
0.01
Variant column describes deleterious (pathological) amino acid substitution in the mutant proteins, MAF – minor allele frequency.
