Assignment of a locus for autosomal dominant idiopathic scoliosis (IS) to human chromosome 17p11

Salehi, Leila; Mangino, Massimo; Serio, Salvatore De; Cicco, D. De; Capon, Francesca; Semprini, Sabrina; Pizzuti, Antonio; Novelli, Giuseppe; Dallapiccola, Bruno

doi:10.1007/s00439-002-0785-4

Cited by 115 publications

(91 citation statements)

References 20 publications

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“…9 A similar study in an Italian family mapped a second locus to 17p11.2 (IS2, MIM 607354). 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.…”

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

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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: 99%

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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“…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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“…The aetiology remains unclear. Previous studies focused on histological factors such as cartilage, skeleton, joint, nerve and muscle but remain inconclusive [2][3][4][5]. In recent years, several studies have indicated that genetic factors play an important role in IS pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…These studies also show a high genetic heterogeneity of either autosomal dominant inheritance with a major gene or multifactorial modes of inheritance. Autosomal dominant [3][4][5], X-linked dominant [6] and multifactorial inheritance [1,7,8] are commonly reported. In this study, we investigated 214 IS families recuited in Southwest Hospital (Chongqing, China) by using the genetic epidemiological method and analysed effects of genetic factors and the mode of inheritance through patients' age, IS incidence, familial aggregation and heritability, as well as traits of hereditary diseases.…”

Section: Introductionmentioning

confidence: 99%

“…Studies showed that these genes are related with IS but cannot explain all IS patients. Chromosomal regions involved in IS susceptibility include 6p, 10q, 18q [21], 6p, 6q, 17p11.2 [5], 8q [22], 9q, 16q [23], 19p13 [3], 19p13.3 [9], 15q25-26 [20], 9q31.2, 9q34.2, 17q25.3-qtel [24], 12p [25] and Xq23-26 [26]. There are considerable numbers of genes in these foci.…”

Section: Introductionmentioning

confidence: 99%

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Epidemiological survey of idiopathic scoliosis and sequence alignment analysis of multiple candidate genes

Yang

QuanZhang

Guo

et al. 2011

International Orthopaedics (SICOT)

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Purpose To investigate the effects of genetic factors on idiopathic scoliosis (IS) and genetic modes through genetic epidemiological survey on IS in Chongqing City, China, and to determine whether SH3GL1, GADD45B, and FGF22 in the chromosome 19p13.3 are the pathogenic genes of IS through genetic sequence analysis. Methods 214 nuclear families were investigated to analyse the age incidence, familial aggregation, and heritability. SH3GL1, GADD45B, and FGF22 were chosen as candidate genes for mutation screening in 56 IS patients of 214 families. The sequence alignment analysis was performed to determine mutations and predict the protein structure. Results The average age of onset of 10.8 years suggests that IS is a early onset disease. Incidences of IS in first-, second-, third-degree relatives and the overall incidence in families (5.68%) were also significantly higher than that of the general population (1.04%). The U test indicated a significant difference, suggesting that IS has a familial aggregation. The heritability of first-degree relatives (77.68 ±10.39%), seconddegree relatives (69.89 ±3.14%), and third-degree relatives (62.14 ±11.92%) illustrated that genetic factors play an important role in IS pathogenesis. The incidence of firstdegree relatives (10.01%), second-degree relatives (2.55%) and third-degree relatives (1.76%) illustrated that IS is not in simple accord with monogenic Mendel's law but manifests as traits of multifactorial hereditary diseases. Sequence alignment of exons of SH3GL1, GADD45B, and FGF22 showed 17 base mutations, of which 16 mutations do not induce open reading frame (ORF) shift or amino acid changes whereas one mutation (C→T)occurred in SH3GL1 results in formation of the termination codon, which induces variation of protein reading frame. Prediction analysis of protein sequence showed that the SH3GL1 mutant encoded a truncated protein, thus affecting the protein structure. Conclusion IS is a multifactorial genetic disease and SH3GL1 may be one of the pathogenic genes for IS.

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Assignment of a locus for autosomal dominant idiopathic scoliosis (IS) to human chromosome 17p11

Cited by 115 publications

References 20 publications

New disease gene location and high genetic heterogeneity in idiopathic scoliosis

New disease gene location and high genetic heterogeneity in 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

Epidemiological survey of idiopathic scoliosis and sequence alignment analysis of multiple candidate genes

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