The Association Analysis of TBX6 Polymorphism With Susceptibility to Congenital Scoliosis in a Chinese Han Population

Qi, Fei; Wu, Zhihong; Wang, Hai; Zhou, Xi; Wang, Naiguo; Ding, Yaozhong; Wang, Yipeng; Qiu, Guixing

doi:10.1097/brs.0b013e3181bc963c

Cited by 41 publications

(35 citation statements)

References 25 publications

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“…In this family no apparent pathogenic mutation of TBX6 gene was detected. But we observed different genotypes at rs2289292 (A/G), a SNP locus which has recently been shown to be associated with congenital scoliosis in Han Chinese [Fei et al, 2010]. The ''A'' genotype in affected proband and the ''G'' genotype in unaffected brother and father is consistent with their finding that ''A'' allele is a significant risk factor of congenital scoliosis.…”

Section: Discussionsupporting

confidence: 90%

Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family

et al. 2010

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The 16p11.2 deletion is a recurrent genomic event and a significant risk factor for autism spectrum disorders (ASD). This genomic disorder also exhibits extensive phenotypic variability and diverse clinical phenotypes. The full extent of phenotypic heterogeneity associated with the 16p11.2 deletion disorder and the factors that modify the clinical phenotypes are currently unknown. Multiplex families with deletion offer unique opportunities for exploring the degree of heterogeneity and implicating modifiers. Here we reported the clinical and genomic characteristics of three 16p11.2 deletion carriers in a Chinese family. The father carries a de novo 16p11.2 deletion, and it was transmitted to the proband and sib. The proband presented with ASD, intellectual disability, learning difficulty, congenital malformations such as atrial septal defect, scoliosis. His dysmorphic features included myopia and strabismus, flat and broad nasal bridge, etc. While the father shared same neurodevelopmental problems as the proband, the younger brother did not show many of the proband's phenotypes. The possible unmasked mutation of TBX6 and MVP gene in this deleted region and the differential distribution of other genomic CNVs were explored to explain the phenotypic heterogeneity in these carriers. This report demonstrated the different developmental trajectory and discordant phenotypes among family members with the same 16p11.2 deletion, thus further illustrated the phenotypic complexity and heterogeneity of the 16p11.2 deletion.

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Section: Discussionsupporting

confidence: 90%

Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family

et al. 2010

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“…46 Additionally, TBX6 polymorphisms were associated with congenital scoliosis in the Han population. 47 In conclusion, our study demonstrates in two independent datasets that the 16p11.2 BP4-BP5 600 kb deletion consistently and quantitatively impacts cognitive functioning, HC, BMI, and growth. A range of behavioural disorders affects the vast majority of carriers.…”

Section: Discussionmentioning

confidence: 56%

A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders

Zufferey¹,

Sherr²,

Beckmann³

et al. 2012

J Med Genet

273

312

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BackgroundThe recurrent ∼600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders.ObjectiveTo define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion.MethodsWe collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls.ResultsWhen compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations.ConclusionsThe 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.

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“…This interval contains the TBX6 gene (OMIM 602427) encoding a sequence-specific DNA transcription factor, which belongs to the T-box gene family [Wilson and Conlon, 2002]. It is known that TBX6 mutations in humans are associated with spondylocostal dysostosis and congenital scoliosis in the Chinese Han population [Fei et al, 2010;Sparrow et al, 2013].…”

Section: Discussionmentioning

confidence: 99%

Sequence Variants in <b><i>TBX6</i></b> Are Associated with Disorders of the Müllerian Ducts: An Update

Tewes¹,

Hucke²,

Römer³

et al. 2019

Sex Dev

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Müllerian anomalies comprise the Mayer-Rokitansky-Küster-Hauser syndrome as well as fusion defects of the müllerian ducts. Recurrent micro-aberrations like deletions in 16p11.2 encompassing TBX6 were found to be causative in these patients. TBX6 encodes a transcription factor which plays a role in paraxial mesoderm differentiation/specification. In previous studies, we and other groups found possibly pathogenic variants in TBX6 in patients with müllerian anomalies. Since we suggested TBX6 as a strong candidate, we performed sequential analysis of the TBX6 gene in additional 125 patients with müllerian anomalies, and 2 possibly pathogenic missense variants and 1 nonsense substitution in TBX6 in 4/125 patients were found. The missense variant c.484G>A, which we have described in a previous study, was reidentified but with no higher frequency as in our controls. We detected 3 possibly pathogenic variants in TBX6 and could show that the variant c.484G>A is not causative for disorders of the müllerian ducts in the non-Finnish European population. In summary, we present increasing evidence for association of variants in TBX6 with malformations of the müllerian ducts.

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The Association Analysis of TBX6 Polymorphism With Susceptibility to Congenital Scoliosis in a Chinese Han Population

Abstract: This is the first report on SNPs of TBX6 gene in CS that suggests genetic variants of TBX6 gene is associated with CS and may play an important role in mediating susceptibility to developing CS in the Chinese Han population.

Cited by 41 publications

References 25 publications

Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family

Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family

A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders

Sequence Variants in <b><i>TBX6</i></b> Are Associated with Disorders of the Müllerian Ducts: An Update

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