A Genetic Locus for Adolescent Idiopathic Scoliosis Linked to Chromosome 19p13.3

Chan, Vivian; Fong, G.C.Y.; Luk, Keith D. K.; Yip, B.; Lee, Miu-Kuen; Wong, Man-Sim; Lu, David; Chan, TK

doi:10.1086/341607

Cited by 142 publications

(107 citation statements)

References 14 publications

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“…A genome-wide scan of seven unrelated multiplex families of Chinese descent with AIS concluded that there was a linkage to chromosome 19p13.3 (IS1, MIM 181800). 8 This finding was replicated in several IS multiplex families in Alden et al's study. 9 A similar study in an Italian family mapped a second locus to 17p11.2 (IS2, MIM 607354).…”

Section: Introductionmentioning

confidence: 66%

New disease gene location and high genetic heterogeneity in idiopathic scoliosis

Edery

Margaritte‐Jeannin

Biot³

et al. 2011

Eur J Hum Genet

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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

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Section: Introductionmentioning

confidence: 66%

New disease gene location and high genetic heterogeneity in idiopathic scoliosis

Edery

Margaritte‐Jeannin

Biot³

et al. 2011

Eur J Hum Genet

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“…Although familial predisposition to scoliosis points unequivocally to genetic background of this condition, the exact mechanism of inheritance still has to be confirmed. The AIS-associated loci were identified on both autosomes [16][17][18] and the X chromosome [19]. Therefore, a polygenic inheritance model with incomplete penetrance and variable expression (DNA methylation) is postulated [3,20,21].…”

Section: Introductionmentioning

confidence: 99%

Participation of sex hormones in multifactorial pathogenesis of adolescent idiopathic scoliosis

Kulis

Goździalska

Drąg

et al. 2015

International Orthopaedics (SICOT)

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Purpose In order to verify the potential association between the aetiopathogenesis of adolescent idiopathic scoliosis (AIS) and the process of sexual maturation, we determined the concentrations of oestrogens in pre-and postmenarcheal girls affected by this condition. AIS, occurring mostly in pubescent girls, is one of the most frequent forms of faulty posture. Therefore, it was assumed that the multifactorial pathomechanism of AIS involves significant deficiency of oestrogens. Methods The diagnosis of AIS was established on the basis of physical examination and analyses of radiograms. Concentrations of FSH, LH, oestrogens, progesterone, osteocalcin and RANKL were determined by ELISA. The activity of alkaline phosphatase (AP) was measured by kinetic method. The study included pre-and postmenarcheal girls with AIS and corresponding groups of scoliosis-free controls. Results In premenarcheal scoliotic girls, the levels of FSH, LH and oestradiol were lower; the levels of progesterone, oestrone and oestriol were higher; and the concentrations of oestrone and oestriol were similar compared to premenarcheal controls. Higher levels of RANKL, osteocalcin and AP were observed in premenarcheal adolescents with AIS compared to controls. The concentrations of FSH, LH, oestradiol, and progesterone in postmenarcheal girls with scoliosis were lower, oestrone were slightly lower and oestriol did not differ compared with the control group. Significantly higher levels of RANKL, osteoc alcin an d A P w ere o bserv ed i n postmenarcheal scoliotic adolescents compared with controls. Conclusions There is an interdependence between the concentration of oestradiol and development of scoliosis. Determination of estradiol may have diagnostic value in the screening of spinal pathologies associated with AIS.

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“…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.…”

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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

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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

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A Genetic Locus for Adolescent Idiopathic Scoliosis Linked to Chromosome 19p13.3

Cited by 142 publications

References 14 publications

New disease gene location and high genetic heterogeneity in idiopathic scoliosis

New disease gene location and high genetic heterogeneity in idiopathic scoliosis

Participation of sex hormones in multifactorial pathogenesis of adolescent idiopathic scoliosis

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

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