Intra-Familial Tests of Association between Familial Idiopathic Scoliosis and Linked Regions on 9q31.3–q34.3 and 16p12.3–q22.2

Miller, Nancy H.; Justice, Cristina M.; Marosy, Beth; Swindle, Kandice; Kim, Yoonhee; Roy-Gagnon, Marie-Hélène; Sung, Heejong; Behneman, Dana; Doheny, Kimberly F.; Pugh, Elizabeth; Wilson, Alexander F.

doi:10.1159/000343751

Cited by 12 publications

(11 citation statements)

References 69 publications

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“…Previous studies suggest that the locus on 16p is a candidate region within a subgroup of families affected with FIS [14,18]. Although multiple TBX6 variants were identified in the families sequenced in this study, none of the TBX6 sequence variants segregated with the FIS phenotype.…”

Section: Discussioncontrasting

confidence: 58%

“…These results identified a significant region on chromosome 16p. Fine-mapping of this region was completed in this AD subset, using custom SNP panels ( Supplemental Table 2 ) [18]. When the affectation status was defined as 20° of lateral spinal curvature, multipoint linkage analyses identified multiple SNPs (27.83 Mb to 31.32 Mb) that were significant at p≤0.001.…”

Section: Resultsmentioning

confidence: 99%

“…Linkage analyses identified a significant candidate region for FIS on 16p in a subset of the initial population identified as most likely exhibiting an AD form of FIS inheritance (95 families, 552 individuals) [14]. Custom SNP fine-mapping panels were generated from National Center for Biotechnology Information (NCBI) dbSNP database (Build 34) to cover the previously identified region of interest on 16p (174 SNPs, spanning approximately 17 megabases (Mb) from 18.1 Mb to 34.8 Mb, dbSNP minor allele frequencies of ≥0.25) [18]. Genotyping was performed on the Illumina BeadArray Platform and evaluated with Illumina's Gentrain software.…”

Section: Methodsmentioning

confidence: 99%

“…A mutation in TBX6 , which results in haploinsufficiency, has been identified as a cause of spondylocostal dysostosis (SCD), a severe syndromic form of congenital vertebral malformations [17]. Through both linkage and association studies in a large FIS population, our own work has identified linkage to chromosome 16p, a locus which contains the TBX6 gene [14,18]. In addition, the 16p11.2 region encompasses several structural variants [19,20].…”

Section: Introductionmentioning

confidence: 99%

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Sequencing of the TBX6 Gene in Families With Familial Idiopathic Scoliosis

et al. 2015

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Study Design A hypothesis-driven study was conducted in a familial cohort to determine the potential association between variants within the TBX6 gene and Familial Idiopathic Scoliosis (FIS). Objective To determine if variants within exons of the TBX6 gene segregate with the FIS phenotype within a sample of families with FIS. Summary of Background Data Idiopathic Scoliosis (IS) is a structural curvature of the spine whose underlying genetic etiology has not been established. IS has been reported to occur at a higher rate than expected in family members of individuals with congenital scoliosis (CS), suggesting that the two diseases might have a shared etiology. The TBX6 gene on chromosome 16p, essential to somite development, has been associated with CS in a Chinese population. Previous studies have identified linkage to this locus in families with FIS, and specifically with rs8060511, located in an intron of the TBX6 gene. Methods Parent-offspring trios from 11 families (13 trios, 42 individuals) with FIS were selected for Sanger sequencing of the TBX6 gene. Trios were selected from a large population of families with FIS in which a genome-wide scan had resulted in linkage to 16p. Results Sequencing analyses of the subset of families resulted in the identification of five coding variants. Three of the five variants were novel; the remaining two variants were previously characterized and account for 90% of the observed variants in these trios. In all cases, there was no correlation between transmission of the TBX6 variant allele and FIS phenotype. However, an analysis of regulatory markers in osteoblasts showed that rs8060511 is in a putative enhancer element. Conclusions Although this study did not identify any TBX6 coding variants that segregate with FIS, we identified a variant that is located in a potential TBX6 enhancer element. Therefore, further investigation of the region is needed.

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Section: Discussioncontrasting

confidence: 58%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sequencing of the TBX6 Gene in Families With Familial Idiopathic Scoliosis

et al. 2015

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“…Esposito et al showed that steroid binding protein polymorphisms were effective in IS development (26). IS related zones were spotted in 6q, 10q and18q, 17p11.2, 19p13.3, 8q11, Xq23-26.1, 9q31.3-q34.3, 5q13-q14 and 3q11-q13, 9q31.2-q34.2, 17q25.3-qtel chromosomes (4, 7, 14, 38,58,68,87,103).…”

Section: Genetic-hormonal Causesmentioning

confidence: 99%

Idiopathic scoliosis

Yaman¹,

Dalbayrak²

2013

Turkish Neurosurgery

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Scoliosis refers to curves exceeding 10 degrees observed through posterioanterior direct radiography. In fact, the diagnosis for idiopathic scoliosis is accepted to exclude already available causes. The aim of this paper was to review the etiopathogenesis, classification systems and the treatment management of idiopathic scoliosis. A search in the National Library of Medicine (Pubmed) database using the key words 'idiopathic' and 'scoliosis' was performed. For the literature review, papers concerning the etiopathogenesis, classification and treatment were selected among these articles. A search in the National Library of Medicine (Pubmed) database using the key words 'idiopathic' and 'scoliosis' yielded 4518 articles published between 1947 and 2013. The main hypothesis put forward included genetic factors, hormonal factors, bone and connective tissue anomalies. King, Lenke, Coonrad and Peking Union Medical College (PUMC) classifications were the main classification systems for idiopathic scoliosis. Exercise, bracing and anterior, posterior or combined surgery when indicated are the choices for the treatment. Every idiopathic scoliosis case has to be managed to its own characteristics. It is the post-operative appearance that the surgeons are perhaps the least interested but the adolescent patients the most interested in. The aim of scoliosis surgery is to restore the spine without neurological deficit.

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Scoliosis and vertebral anomalies: Additional abnormal phenotypes associated with chromosome 16p11.2 rearrangement

Al-Kateb

Khanna

Filges

et al. 2014

American J of Med Genetics Pt A

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The typical chromosome 16p11.2 rearrangements are estimated to occur at a frequency of approximately 0.6% of all samples tested clinically and have been identified as a major cause of autism spectrum disorders, developmental delay, behavioral abnormalities, and seizures. Careful examination of patients with these rearrangements revealed association with abnormal head size, obesity, dysmorphism, and congenital abnormalities. In this report, we extend this list of phenotypic abnormalities to include scoliosis and vertebral anomalies. We present detailed characterization of phenotypic and radiological data of 10 new patients, nine with the 16p11.2 deletion and one with the duplication within the coordinates chr16:29,366,195 and 30,306,956 (hg19) with a minimal size of 555 kb. We discuss the phenotypical and radiological findings in our patients and review 5 previously reported patients with 16p11.2 rearrangement and similar skeletal abnormalities. Our data suggest that patients with the recurrent 16p11.2 rearrangement have increased incidence of scoliosis and vertebral anomalies. However, additional studies are required to confirm this observation and to establish the incidence of these anomalies. We discuss the potential implications of our findings on the diagnosis, surveillance and genetic counseling of patients with 16p11.2 rearrangement.

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Intra-Familial Tests of Association between Familial Idiopathic Scoliosis and Linked Regions on 9q31.3–q34.3 and 16p12.3–q22.2

Cited by 12 publications

References 69 publications

Sequencing of the TBX6 Gene in Families With Familial Idiopathic Scoliosis

Sequencing of the TBX6 Gene in Families With Familial Idiopathic Scoliosis

Idiopathic scoliosis

Scoliosis and vertebral anomalies: Additional abnormal phenotypes associated with chromosome 16p11.2 rearrangement

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