Assignment of two loci for autosomal dominant adolescent idiopathic scoliosis to chromosomes 9q31.2-q34.2 and 17q25.3-qtel

Ocaka, Louise; Zhao, Chengfeng; Reed, Johanna A.; Ebenezer, Neil D.; Brice, Glen; Morley, Timothy; Mehta, M. H.; O’Dowd, John; Weber, James L.; Hardcastle, Alison J.; Child, Anne H.

doi:10.1136/jmg.2007.051896

Cited by 72 publications

(58 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…10 Another study reported on the mapping of two loci for IS on chromosome 9q31.2-q34.2 (IS4, MIM 612238) and 17q25.3-qtel (IS5, MIM 612239), the latter by combining information obtained from two unrelated IS families. 11 Recently, a locus for IS and pectus excavatum was found in a single large family on chromosome 18q. 12 In the present study, we performed model-dependent linkage analyses in three large IS families compatible with autosomal dominant inheritance of the disease trait with a high number of informative meioses.…”

Section: Introductionmentioning

confidence: 99%

New disease gene location and high genetic heterogeneity in idiopathic scoliosis

Edery

Margaritte‐Jeannin

Biot³

et al. 2011

Eur J Hum Genet

View full text Add to dashboard Cite

International audienceIdiopathic scoliosis is a spine disorder of unknown origin with 1.5-3% prevalence in the general population. Besides the large multifactorial form sample of idiopathic scoliosis, there is a good evidence for the existence of a monogenic subgroup in which the disease is inherited in a dominant manner. However, results from literature suggest a strong heterogeneity in the locations of the mutated genes. Using a high resolution genome-wide scan, we performed linkage analyses in three large multigenerational idiopathic scoliosis families compatible with dominant inheritance including 9 to 12 affected members or obligate carriers. In two of these families, our results suggested intra-familial genetic heterogeneity whereas, in the other, we observed a perfect marker disease co-segregation in two regions at 3q12.1 and 5q13.3. We can state that one of these two locations is a novel idiopathic scoliosis disease gene locus, since the probability of having this perfect co-segregation twice by chance in the genome is very low (p=0.001). Lastly, in all three families studied, linkage to the previously mapped dominant idiopathic scoliosis loci on chromosomes 19p13.3, 17p11.2, 9q34, 17q25 and 18q is unlikely, confirming that there is a high genetic heterogeneity within the subgroup of dominant forms of idiopathic scoliosis

show abstract

Section: Introductionmentioning

confidence: 99%

New disease gene location and high genetic heterogeneity in idiopathic scoliosis

Edery

Margaritte‐Jeannin

Biot³

et al. 2011

Eur J Hum Genet

View full text Add to dashboard Cite

show abstract

“…[5][6][7][8] Genome-wide linkage analyses have identified susceptibility loci on chromosome 6p, 8q12, 9q31.2-q34.2, 10q, 12p, 17p11, 17q25.30-qtel, 18q, 19p13 and chromosome X. [9][10][11][12][13][14][15][16] Several candidate gene studies have also reported that genes such as COL1A1, COL1A2, FBN1, ESR, MATN1, MTNR1B, CHD7, VDR and GPER were associated with scoliosis. 10,[17][18][19][20][21][22][23][24] Recently, a genome-wide association study (GWAS) has been applied to identify the susceptibility loci of AIS.…”

Section: Introductionmentioning

confidence: 99%

SNP rs11190870 near LBX1 is associated with adolescent idiopathic scoliosis in southern Chinese

et al. 2012

View full text Add to dashboard Cite

A study was conducted to validate the most significant single nucleotide polymorphism (SNP) from a genome-wide association study of Japanese adolescent idiopathic scoliosis (AIS) patients in an independent southern Chinese population. In total, 300 AIS patients fulfilled the clinical criteria and 788 controls with MRI scans of the spine were included in the replication study. We employed case-control analysis to study the association of SNP rs11190870 near LBX1 (ladybird homeobox 1) with AIS in a southern Chinese population. The results suggest that SNP rs11190870 is significantly associated with AIS (P¼9.1Â10 À10 ; odds ratio¼1.85; 95% confidence interval¼1.52-2.25). The results of this study confirm that SNP rs11190870 is associated with AIS. Keywords: adolescent idiopathic scoliosis; replication study; rs11190870; southern Chinese INTRODUCTIONThe most common form of scoliosis is adolescent idiopathic scoliosis (AIS). AIS affects 1-4% of children aged between 10 and 16 years, 1,2 and affects more females than males. 3,4 It is known that the inheritance of AIS is complex. The role of genetic factors in scoliosis is well-documented and widely accepted. 5-8 Genome-wide linkage analyses have identified susceptibility loci on chromosome 6p, 8q12, 9q31.2-q34. 2, 10q, 12p, 17p11, 17q25.30-qtel, 18q, 19p13 and chromosome X. 9-16 Several candidate gene studies have also reported that genes such as COL1A1, COL1A2, FBN1, ESR, MATN1, MTNR1B, CHD7, VDR and GPER were associated with scoliosis. 10,[17][18][19][20][21][22][23][24] Recently, a genome-wide association study (GWAS) has been applied to identify the susceptibility loci of AIS. 25 The single nucleotide polymorphism (SNP) rs11190870 that is located in the 3¢-flanking region of LBX1 (ladybird homeobox 1) gene at chromosome 10q24.31 was identified as the most significant common variant in Japanese females with P¼1.24Â10 19 ; odds ratio (OR)¼1.56. 25 In the present study, we conducted a study to validate the association of rs11190870 with AIS in an independent southern Chinese population that contains 300 cases and 788 controls. Our results suggest that the SNP rs11190870 is highly significantly associated with AIS. MATERIALS AND METHODS SubjectsInformed consent was obtained from all individuals participating in this study. A cohort consisting of 300 AIS patients was recruited at the Duchess of Kent Children's Hospital in Hong Kong. The patient selection criteria for the study are as follows: (1) Patients with idiopathic scoliosis deformity involving the thoracic plus or minus the lumbar spine with Cobb's angles more than 35 degrees and required surgical operations in Duchess of Kent Children's Hospital. (2) The onset of scoliosis deformity was after 10 years and under 20 years of age. (3) Neuromuscular, congenital and syndromal scoliosis individuals were excluded by history taking, physical examination and X-ray of the spine. The control samples were from a large data set of southern Chinese population (3500 samples) recruited for a study on the genetics of degenera...

show abstract

“…5 Inoue et al 6 reported AIS concordance rates as 92.3% in monozygotic twins, and 62.5% in dizygotic twins. Recent genome-wide linkage analyses have identified many predisposing loci of AIS, [7][8][9][10][11][12][13][14][15][16] further supporting a role of genetic factor(s) in AIS. Single nucleotide polymorphisms (SNPs) in the genes for estrogen receptor 1 (ESR1), 17 estrogen receptor 2 (ESR2), 18 matrilin 1 (MATN1), 19 melatonin receptor 1B (MTNR1B), 20 and tryptophan hydroxylase 1 (TPH1) 21 are reported to be associated with AIS predisposition.…”

mentioning

confidence: 99%

Lack of association between adolescent idiopathic scoliosis and previously reported single nucleotide polymorphisms in MATN1, MTNR1B, TPH1, and IGF1 in a Japanese population

Takahashi

Matsumoto

Karasugi

et al. 2011

Journal Orthopaedic Research

View full text Add to dashboard Cite

Adolescent idiopathic scoliosis (AIS) is a spinal deformity most commonly arising in apparently healthy girls around puberty. AIS has a strong genetic predisposition. Several genetic associations between AIS and single nucleotide polymorphisms (SNPs) have been reported; common SNPs in the genes for matrilin 1 (MATN1), melatonin receptor 1B (MTNR1B), tryptophan hydroxylase 1 (TPH1), and insulin-like growth factor 1 (IGF1) are reported to be associated with AIS in Chinese. However, these associations have not been replicated so far. To confirm the associations, we compared these SNPs with AIS predisposition and curve severity in a population of Japanese females consisting of 798 AIS patients and 1,239 controls. All the subjects were genotyped using the PCR-based Invader assay. We found no association of any of the SNPs with AIS predisposition or curve severity. Considering the statistical power and sample size of the present study, we concluded that these SNPs are not associated with either AIS predisposition or curve severity in Japanese. ß

show abstract

Assignment of two loci for autosomal dominant adolescent idiopathic scoliosis to chromosomes 9q31.2-q34.2 and 17q25.3-qtel

Abstract: This study reports a common locus for AIS in the British population, mapping to a refined interval on chromosome 9q31.2-q34.2 and defines a novel AIS locus on chromosome 17q25.3-qtel.

Cited by 72 publications

References 26 publications

New disease gene location and high genetic heterogeneity in idiopathic scoliosis

New disease gene location and high genetic heterogeneity in idiopathic scoliosis

SNP rs11190870 near LBX1 is associated with adolescent idiopathic scoliosis in southern Chinese

Lack of association between adolescent idiopathic scoliosis and previously reported single nucleotide polymorphisms in MATN1, MTNR1B, TPH1, and IGF1 in a Japanese population

Contact Info

Product

Resources

About