Deciphering the etiology of congenital scoliosis: A genetic and epigenetic perspective

Table 1 Genes associated with congenital scoliosis

Gene name	Gene function	Associated research	Mutation type	Associated clinical manifestations	Ref.
FGFR1	Involved in early human embryo development and plays an important role in the formation of protoganglionic embryos, organ specification and tissue patterning	Mutations are associated with CS and skeletal phenotypes	Shift code variants, missense variants	Vertebral malformations, and scoliosis	[22]
TBXT	Plays a crucial role in embryonic development, especially in mesoderm formation, notochord development, somite formation, and neural tube closure	Mutations are associated with a wide range of congenital malformations, especially developmental abnormalities of the spine and nervous system	Missense mutations	Scoliosis	[27,28]
TBX6	Transcription factor involved in mesodermal development	Associated with genetic variation in spinal development	Nonsense mutations, code-shifting mutations	Scoliosis and other deformities	[11,29,31]
GDF3	Plays an important role in skeletal development and morphogenesis	Genetic variants are associated with multiple skeletal disorders	Missense mutations	Scoliosis, congenital skeletal malformations	[35]
PTK7	Regulates embryonic and skeletal development	Associated with scoliosis	Shifted code mutation, missense mutation	Scoliosis, skeletal deformities	[36]
DLL3	Plays a role in cell-cell interactions	Mutations associated with spinal dysplasia	Deletion mutations	In spinal dysplasia	[42]
HES7	Involved in vertebral development and differentiation	Mutation is associated with scoliosis and other spinal deformities	Point mutations	Abnormalities in spinal structure	[39,43]
LFNG	Involved in the regulation of cell signaling and development, with important roles primarily in the spinal cord and central nervous system	Mutations are strongly associated with specific scoliosis phenotypes	Missense mutations	Scoliosis, vertebral deformities and multiple rib deformities	[47]
COL11A2	Development of the spine and joints	Associated with multiple spine-related disorders such as scoliosis and other skeletal developmental abnormalities	Nonsense mutations	Scoliosis and other skeletal developmental abnormalities	[48]
DSTYK	Involved in the regulation of cell signaling and developmental processes, particularly important during embryonic development	Associated with scoliosis	Missing variant	Scoliosis, spinal dysplasia, skeletal deformities	[49]
SOX9	Promotes chondrocyte differentiation during embryonic development	Mutations are associated with the development of several genetic syndromes and spinal deformities		Scoliosis	[37]
DHX40	Plays an important role in the regulation of gene expression	Mutations associated with scoliosis		Scoliosis, other congenital malformations	[50]
NBPF20	Involved in the regulation of gene expression, cell differentiation and development	Mutation associated with scoliosis		Scoliosis	[50]

FGFR1: Fibroblast growth factor receptor 1; TBXT: T-box transcription factor T; TBX6: T-box transcription factor 6; GDF3: Growth differentiation factor 3; PTK7: Protein tyrosine kinase 7; DLL3: Delta like canonical Notch ligand 3; HES7: Hes family bHLH transcription factor 7; LFNG: Lunatic Fringe; COL11A2: Collagen type XI alpha 2 chain; DSTYK: Dual serine/threonine and tyrosine protein kinase; SOX9: SRY-box transcription factor 9.