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

Abstract 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.

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

10.21203/rs.3.rs-46911/v1 ◽

2020 ◽

Author(s):

Xiaowen Xu ◽

Binbin Wang ◽

Yufan Chen ◽

Weizheng Zhou ◽

Lianyong Li

Keyword(s):

Sanger Sequencing ◽

Transmembrane Protein ◽

Hip Dislocation ◽

Developmental Dysplasia ◽

Chinese Han Population ◽

Reference Sequence ◽

Chinese Han ◽

Han Population ◽

Joint Deformity ◽

Dysplasia Of The Hip

Abstract 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.

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

10.21203/rs.3.rs-46911/v2 ◽

2020 ◽

Author(s):

Xiaowen Xu ◽

Binbin Wang ◽

Yufan Chen ◽

Weizheng Zhou ◽

Lianyong Li

Keyword(s):

Sanger Sequencing ◽

Transmembrane Protein ◽

Hip Dislocation ◽

Developmental Dysplasia ◽

Chinese Han Population ◽

Reference Sequence ◽

Chinese Han ◽

Han Population ◽

Joint Deformity ◽

Dysplasia Of The Hip

Abstract 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.

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A Replication Study for the Association of rs726252 in PAPPA2 with Developmental Dysplasia of the Hip in Chinese Han Population

BioMed Research International ◽

10.1155/2014/979520 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 4

Author(s):

Dongquan Shi ◽

Wei Sun ◽

Xingquan Xu ◽

Zheng Hao ◽

Jin Dai ◽

...

Keyword(s):

Hip Dislocation ◽

Developmental Dysplasia ◽

Replication Study ◽

Chinese Han Population ◽

Taqman Assay ◽

Genotype Distribution ◽

Chinese Han ◽

Han Population ◽

Significant Difference ◽

Dysplasia Of The Hip

Developmental dysplasia of the hip (DDH) is a common developmental hip disorder, which ranges from mild acetabulum malformation to irreducible hip dislocation. A previous study suggested a significant association of pregnancy-associated plasma protein-A2 (PAPPA2) with DDH susceptibility in Chinese Han population. But with the consideration of the sample size, the association was still debatable. To confirm the association of the reported single nucleotide polymorphism (SNP) in PAPPA2, rs726252 with DDH, we conducted a case-control study in a larger number of subjects. We genotyped rs726252 in 697 DDH subjects and 707 control subjects by TaqMan assay. The association between this SNP and DDH was evaluated statistically. No significant difference was found in any comparison of genotype distribution nor allele frequency between cases and controls. Our replication study indicated that the association between rs726252 and DDH in Chinese Han population was debatable. The association between PAPPA2 and DDH should be evaluated by additional studies.

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Lack of evidence for association between DVWA gene polymorphisms and developmental dysplasia of the hip in Chinese Han population

Rheumatology International ◽

10.1007/s00296-010-1410-9 ◽

2010 ◽

Vol 31 (7) ◽

pp. 883-887 ◽

Cited By ~ 6

Author(s):

Lunqing Zhu ◽

Dongquan Shi ◽

Jin Dai ◽

Jianghui Qin ◽

Jianbo Fan ◽

...

Keyword(s):

Gene Polymorphisms ◽

Developmental Dysplasia ◽

Chinese Han Population ◽

Chinese Han ◽

Han Population ◽

Dysplasia Of The Hip

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Genetic variant of COL11A2 gene is functionally associated with developmental dysplasia of the hip in Chinese Han population

Aging ◽

10.18632/aging.103040 ◽

2020 ◽

Vol 12 (9) ◽

pp. 7694-7703

Author(s):

Renjie Xu ◽

Xin Jiang ◽

Junlan Lu ◽

Kexin Wang ◽

Ye Sun ◽

...

Keyword(s):

Genetic Variant ◽

Developmental Dysplasia ◽

Chinese Han Population ◽

Chinese Han ◽

Han Population ◽

Dysplasia Of The Hip ◽

Col11a2 Gene

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Mutation screening of the UBE3A gene in Chinese Han population with autism

10.21203/rs.3.rs-40284/v1 ◽

2020 ◽

Author(s):

Xue Zhao ◽

Ran Zhang ◽

Shunying Yu

Keyword(s):

Sample Size ◽

Sanger Sequencing ◽

Autism Spectrum ◽

Chinese Han Population ◽

Control Groups ◽

Chinese Han ◽

Han Population ◽

Coding Regions ◽

Genotype Frequencies ◽

And Control

Abstract Background 15q11-13 region is one of the most complex chromosomal regions in the human genome. UBE3A is an important candidate gene of autism spectrum disorder (ASD), which located at the 15q11-13 region and encodes ubiquitin-protein ligase E3A. Previous studies about UBE3A gene and ASD have shown inconsistent results and few studies were performed in Chinese population. This study aimed to detect the genetic variation of UBE3A gene in Chinese Han population with ASD and analyze the genetic association between these variations and ASD. Methods The samples consisted of 192 patients with clinical diagnosis of autism according to the DSM-IV diagnostic criteria and 192 healthy controls. We searched for mutations at coding sequence (CDS) regions and their adjacent non-coding regions of UBE3A gene using the high resolution melting (HRM) and Sanger sequencing methods. We further increased sample size to validate the detected variants using HRM and analyzed the difference of allele and genotype frequencies between case and control groups. Results A known single nucleotide polymorphism (T > C, rs150331504) located at the CDS4 and a known 5 bp insertion/deletion variation (AACTC+/-, rs71127053) located at the intron region of the upstream 288 bp of the CDS2 of UBE3A gene were detected using Sanger sequencing method. The association analysis suggested that there were no significant difference about the allele and genotype frequencies of rs71127053 and rs150331504 between case and control groups after extending the sample size. Besides, rs150331504 is a synonymous mutation and we analyzed the minimum free energy (MFE) of mRNA coded by the different alleles of rs150331504. The result showed that MFE values of the allele T and allele C of rs150331504 were different and indicated that the variant might alter the mRNA secondary structure. We did not detect mutations in other coding regions of UBE3A gene. Conclusions These findings showed that UBE3A gene might not be a major disease gene in Chinese ASD cases.

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CLINICAL AND GENETIC CHARACTERISTICS OF 17α-HYDROXYLASE/17, 20-LYASE DEFICIENCY: c.985_987delTACinsAA MUTATION OF CYP17A1 PREVALENT IN CHINESE HAN POPULATION

Endocrine Practice ◽

10.4158/ep-2020-0478 ◽

2020 ◽

Author(s):

Junke Xia ◽

Furong Liu ◽

Jing Wu ◽

Yanjie Xia ◽

Zhenhua Zhao ◽

...

Keyword(s):

Cytochrome P450 ◽

In Silico ◽

Sanger Sequencing ◽

Chinese Han Population ◽

Genetic Mutations ◽

Sry Gene ◽

Chinese Han ◽

Genetic Characteristics ◽

Han Population ◽

Lyase Deficiency

Backgrounds: 17α-hydroxylase/17, 20-lyase deficiency (17-OHD) is a rare recessive hereditary disease, which could be attributed to cytochrome P450 17 α-hydroxylase (P450c17) deficiency caused by CYP17A1 gene mutations. Methods : A large cohort of 10 Chinese Han patients with 17-OHD from 2012 to 2020 were enrolled. The clinical and biochemical features were investigated and genetic mutations of CYP17A1 were analyzed by PCR-Sanger sequencing. Karyotype identification and SRY gene test were also carried out. In-silico analysis was used to predict the effects of genetic mutations on the protein function. Results: Gender was female in all the patients. The common complaints were hypertension, hypokalemia and primary amenorrhea. Karyotype was 46, XY and SRY gene was detected in 7 patients, and karyotype was XX in the remaining 3 patients. A total of 7 mutations including Y329N, Y329*, Y329Lfs*, R96W, A82D, S380N and A487_P489del have been identified in CYP17A1 gene. Y329Lfs* mutation was found in 9/10 (90%) patients with a high allele frequency of 70%. In-silico prediction showed that a novel variant of c.1139G>A (S380N) occurred at a conserved residue and should be disease-causing. Conclusion: We presented a detailed description of the clinical and genetic characteristics in Chinese patients with 17-OHD, and concluded that Y329Lfs* mutation of CYP17A1 prevalent in Chinese Han population. Therefore, hotspot screening by PCR-Sanger sequencing for exon 6 of CYP17A1 could contribute to the rapid diagnosis of 17-OHD in China. Genetic counseling based on the genetic diagnosis for at-risk relatives is advised. Abbreviations: 17-OHD = 17α-hydroxylase/17, 20-lyase deficiency; 17a-OHP= 17ahydroxyprogesterone; ACTH= adrenocorticotropic hormone; ACMG= American College of Medical Genetics and Genomics; CAH= congenital adrenal hyperplasia; CT= computed tomography; CYP17A1= cytochrome P450 family 17 subfamily A member 1 gene; DHEAS= dehydroepiandrosterone sulfate; EV= estradiol valerate tablets; HC= hydrocortisone; HGMD= Human Gene Mutation Database; P450c17= P450 17 α-hydroxylase; PCR= Polymerase chain reaction; PRED= prednisone; UFC= 24-h urinary free cortisone; SRY= sex-determining region Y gene.

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