Developmental Dysplasia of the Hip: A Review of Etiopathogenesis, Risk Factors, and Genetic Aspects

et al. 2021

Ital J Pediatr

Background Developmental dysplasia of the hip (DDH) is a complex hip joint deformity with effects ranging from acetabulum malformation to irreversible hip dislocation. Previous studies suggest a significant association of four variations, teneurin transmembrane protein 3 (TENM3, OMIM * 610083) (chr4:183721398), heparan sulfate proteoglycan 2 (HSPG2, OMIM * 142461) (chr1:22201470), ATPase plasma membrane Ca2+ transporting 4 (ATP2B4, OMIM * 108732) (chr1:203682345), and prostaglandin F receptor (PTGFR, OMIM * 600563) (chr1:79002214), with DDH susceptibility in families with segregating DDH. However, the association was not validated in sporadic cases and remains controversial. To confirm the association of the reported variations in these four genes with DDH, we conducted replicative verification in 250 sporadic samples with DDH from a Chinese Han population. Methods We conducted Sanger sequencing after amplifying the variation sites. The results were compared with the reference sequence from the GRCh37 assembly in UCSC (http://genome.ucsc.edu). Results Replication analysis of 250 sporadic samples by Sanger sequencing indicated that the four variations, TENM3 (OMIM * 610083, chr4:183721398), HSPG2 (OMIM * 142461, chr1:22201470), ATP2B4 (OMIM * 108732, chr1:203682345), and PTGFR (OMIM * 600563, chr1:79002214), were not associated with the susceptibility to DDH in the Chinese Han population. Conclusions Further studies should be performed to identify other variations of these four genes that are potentially associated with DDH by whole-exome sequencing and the results should be verified in different populations.

Section: Introductionmentioning

confidence: 99%

“…DDH is a polygenic disease with complex genetic causes [ 10 ]. A series of studies on C-X3-C motif chemokine receptor 1 ( CX3CR1, OMIM * 601470) provided methods for identifying DDH-related genes.…”

Section: Introductionmentioning

confidence: 99%

Replicative verification of susceptibility genes previously identified from families with segregating developmental dysplasia of the hip

Wang²,

et al. 2021

Ital J Pediatr

“…However, the pathogenic genes causing DDH are yet to be identi ed [6]. Several genes, including WNT inhibitory factor 1 (WIF1), Collagen type XI alpha 2 chain (COL11A2), and Pregnancy-associated plasma protein A2 (PAPPA2), were shown to increase susceptibility to DDH through candidate association studies in one population [7][8][9][10]. However, these results could not be con rmed in other populations.…”

Section: Introductionmentioning

confidence: 99%

“…DDH is a polygenic disease with complex genetic causes [10]. A series of studies on C-X3-C motif chemokine receptor 1 (CX3CR1) provided methods for identifying DDH-related genes.…”

Section: Introductionmentioning

confidence: 99%

Replicative Verification of Susceptibility Genes Previously Identified from Families with Segregating Developmental Dysplasia of the Hip

Wang²,

et al. 2020

Preprint

Background: Developmental dysplasia of the hip (DDH) is a complex hip joint deformity with effects ranging from acetabulum malformation to irreversible hip dislocation. Previous studies suggest a significant association of four variations, Teneurin transmembrane protein 3 (TENM3) (chr4:183721398), Heparan sulfate proteoglycan 2 (HSPG2) (chr1:22201470), ATPase plasma membrane Ca2+ transporting 4 (ATP2B4) (chr1:203682345), and Prostaglandin F receptor (PTGFR) (chr1:79002214), with DDH susceptibility in families with segregating DDH. However, the association was not validated in sporadic cases and remains controversial. To confirm the association of the reported variations in these four genes with DDH, we conducted replicative verification in 250 sporadic samples with DDH from a Chinese Han population. Methods: We conducted Sanger sequencing after amplifying the variation sites. The results were compared with the reference sequence from the GRCh37 assembly in UCSC (http://genome.ucsc.edu). Results: Replication analysis of 250 sporadic samples by Sanger sequencing indicated that the four variations, TENM3 (chr4:183721398), HSPG2 (chr1:22201470), ATP2B4 (chr1:203682345), and PTGFR (chr1:79002214), were not associated with the susceptibility to DDH in the Chinese Han population.Conclusions: Further studies should be performed to identify other variations of these four genes that are potentially associated with DDH by whole-exome sequencing and the results should be verified in different populations.

“…However, the pathogenic genes causing DDH are yet to be identi ed [6]. Several genes, including WNT inhibitory factor 1 (WIF1, OMIM * 605186), Collagen type XI alpha 2 chain (COL11A2, OMIM * 120290), and Pregnancy-associated plasma protein A2 (PAPPA2 OMIM * 176385 ), were shown to increase susceptibility to DDH through candidate association studies in one population [7][8][9][10]. However, these results could not be con rmed in other populations.…”

Section: Introductionmentioning

confidence: 99%

Replicative Verification of Susceptibility Genes Previously Identified from Families with Segregating Developmental Dysplasia of the Hip

Wang²,

et al. 2020

Preprint

Background: Developmental dysplasia of the hip (DDH) is a complex hip joint deformity with effects ranging from acetabulum malformation to irreversible hip dislocation. Previous studies suggest a significant association of four variations, teneurin transmembrane protein 3 (TENM3, OMIM * 610083) (chr4:183721398), heparan sulfate proteoglycan 2 (HSPG2, OMIM * 142461 ) (chr1:22201470), ATPase plasma membrane Ca2+ transporting 4 (ATP2B4, OMIM * 108732) (chr1:203682345), and prostaglandin F receptor (PTGFR, OMIM * 600563) (chr1:79002214), with DDH susceptibility in families with segregating DDH. However, the association was not validated in sporadic cases and remains controversial. To confirm the association of the reported variations in these four genes with DDH, we conducted replicative verification in 250 sporadic samples with DDH from a Chinese Han population. Methods: We conducted Sanger sequencing after amplifying the variation sites. The results were compared with the reference sequence from the GRCh37 assembly in UCSC (http://genome.ucsc.edu). Results: Replication analysis of 250 sporadic samples by Sanger sequencing indicated that the four variations, TENM3 (OMIM * 610083, chr4:183721398), HSPG2 (OMIM * 142461, chr1:22201470), ATP2B4 (OMIM * 108732, chr1:203682345), and PTGFR (OMIM * 600563, chr1:79002214), were not associated with the susceptibility to DDH in the Chinese Han population.Conclusions: Further studies should be performed to identify other variations of these four genes that are potentially associated with DDH by whole-exome sequencing and the results should be verified in different populations.