Variations in RBM8A and TBX6 are associated with disorders of the müllerian ducts

Tewes, Ann‐Christin; Rall, Kristin Katharina; Römer, Thomas; Hucke, J.; Kapczuk, Karina; Brucker, Sara Y.; Ledig, Susanne

doi:10.1016/j.fertnstert.2015.02.014

Cited by 40 publications

(50 citation statements)

References 31 publications

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“…Summing up with our previous study [Tewes et al, 2015], we found in our 2 studies in 5 of 292 ( ∼ 1.7%) patients with malformations of the müllerian ducts 4 different and possibly disease-causing sequence variants in the TBX6 gene. Furthermore, we found the sequence variant c.484G>A in 11 of 292 of the patients and also in 4 of 135 of the control samples.…”

Section: Discussionsupporting

confidence: 83%

“…Furthermore, Sand-backa et al [2013] also found it in a homozygous state in 2.7% and in a heterozygous state in 10.7% in a cohort of Finish patients with müllerian aplasia ( n = 112) and in addition in 4% of the control group ( n = 200). We found this variant in a previous study [Tewes et al, 2015] in a heterozygous state in 3% (5/167) and in this study in 4.8% (6/125) of the patients with malformations of the mülle-rian ducts -in summary in 3.8% (11/292) of the analyzed patients.…”

Section: Discussionsupporting

confidence: 72%

“…The sequence variant c.484G>A (p.Gly162Ser; rs56098093), which we already found in our previous study [Tewes et al, 2015], was detected in 6 patients of whom 2 patients carry another TBX6 variant: 4 patients with fusion anomalies of the müllerian ducts, 1 patient with MRKHS type 1, and 1 patient with MRKHS type 2, respectively. The 4 patients with fusion anomalies of the müllerian ducts include 1 patient with HWWS, 1 with a unicornuate uterus, and 2 patients with a septate uterus.…”

Section: Discussionsupporting

confidence: 63%

“…We concluded that variants of the TBX6 gene seem to be associated with disorders of the müllerian ducts [Tewes et al, 2015].…”

Section: Discussionmentioning

confidence: 82%

“…Recently, in a previous study we found 2 different heterozygous and possibly pathogenic missense variants in TBX6 (c.1015C>A, p.Pro339Thr; c.484G>A, p.Gly162Ser) in a cohort of 167 patients with malformations of the müllerian ducts. The variant c.484G>A has been thought to be associated with malformations of the müllerian ducts [Sandbacka et al, 2013;Tewes et al, 2015]. Therefore, we concluded that variants in TBX6 are associated with malformations of the müllerian ducts.…”

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confidence: 73%

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Sequence Variants in TBX6 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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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 72%

Section: Discussionsupporting

confidence: 63%

“…We concluded that variants of the TBX6 gene seem to be associated with disorders of the müllerian ducts [Tewes et al, 2015].…”

Section: Discussionmentioning

confidence: 82%

mentioning

confidence: 73%

See 3 more Smart Citations

Sequence Variants in TBX6 Are Associated with Disorders of the Müllerian Ducts: An Update

Tewes¹,

Hucke²,

Römer³

et al. 2019

Sex Dev

Self Cite

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Etiologies of uterine malformations

Jacquinet

Millar

Lehman

2016

American J of Med Genetics Pt A

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Ranging from aplastic uterus (including Mayer-Rokitansky-Kuster-Hauser syndrome) to incomplete septate uterus, uterine malformations as a group are relatively frequent in the general population. Specific causes remain largely unknown. Although most occurrences ostensibly seem sporadic, familial recurrences have been observed, which strongly implicate genetic factors. Through the study of animal models, human syndromes, and structural chromosomal variation, several candidate genes have been proposed and subsequently tested with targeted methods in series of individuals with isolated, non-isolated, or syndromic uterine malformations. To date, a few genes have garnered strong evidence of causality, mainly in syndromic presentations (HNF1B, WNT4, WNT7A, HOXA13). Sequencing of candidate genes in series of individuals with isolated uterine abnormalities has been able to suggest an association for several genes, but confirmation of a strong causative effect is still lacking for the majority of them. We review the current state of knowledge about the developmental origins of uterine malformations, with a focus on the genetic variants that have been implicated or associated with these conditions in humans, and we discuss potential reasons for the high rate of negative results. The evidence for various environmental and epigenetic factors is also reviewed. © 2016 Wiley Periodicals, Inc.

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TBX6 as a cause of a combined skeletal‐kidney dysplasia syndrome

Strong

Wang

et al. 2022

American J of Med Genetics Pt A

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TBX6 encodes transcription‐factor box 6, a transcription factor critical to paraxial mesoderm segmentation and somitogenesis during embryonic development. TBX6 haploinsufficiency is believed to drive the skeletal and kidney phenotypes associated with the 16p11.2 deletion syndrome. Heterozygous and biallelic variants in TBX6 are associated with vertebral and rib malformations (TBX6‐associated congenital scoliosis) and spondylocostal dysostosis, and heterozygous TBX6 variants are associated with increased risk of genitourinary tract malformations. Combined skeletal and kidney phenotypes in individuals harboring heterozygous or biallelic TBX6 variants are rare. Here, we present seven individuals with vertebral and rib malformations and structural kidney differences associated with heterozygous TBX6 gene deletion in trans with a hypomorphic TBX6 allele or biallelic TBX6 variants. Our case series highlights the association between TBX6 and both skeletal and kidney disease.

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Variations in RBM8A and TBX6 are associated with disorders of the müllerian ducts

Cited by 40 publications

References 31 publications

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

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

Etiologies of uterine malformations

TBX6 as a cause of a combined skeletal‐kidney dysplasia syndrome

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