Duplication of <i>SOX3</i> (Xq27) may be a risk factor for Neural Tube Defects

Uguen, Arnaud; Talagas, Matthieu; Redon, Sylvia; Marcorelles, Pascale; Braekeleer, Marc De

doi:10.1002/ajmg.a.37072

Cited by 11 publications

(17 citation statements)

References 4 publications

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“…These data provided preliminary evidence that upregulation of SOX3 due to duplication may constitute a risk factor for NTD . This hypothesis was reinforced later by the report of two male sibling fetuses with spina bifida carrying a 395‐kb Xq27 microduplication, which included SOX3 as the sole gene . Here, we detected submicroscopic duplications of the Xq chromosome encompassing the SOX3 gene in two female fetuses.…”

Section: Discussionsupporting

confidence: 68%

“…Interestingly, structural rearrangements involving SOX3 have also been described in patients with XX male sex reversal or ovotesticular disorder of sex development . More recently, increased expression of SOX3 by gene duplication has been proposed as a risk factor for NTDs in both sexes …”

Section: Discussionmentioning

confidence: 99%

“…Moreover, several patients and fetuses presenting myelomeningocele (MMC) and Xq27 duplications have been reported . Recently, the critical region was narrowed down to a 395‐kb segment that includes only the SOX3 gene, incriminating this genomic imbalance as a predisposing factor for NTDs . Here, we report our detection, using chromosomal microarray analysis (CMA), of two cases of SOX3 microduplication in fetuses with MMC.…”

Section: Introductionmentioning

confidence: 93%

“…In about 10% of cases, NTDs can be associated with genetic disorders such as Fraser syndrome, Meckel‐Gruber syndrome, or Walker‐Warburg syndrome or chromosomal anomalies such as trisomy 18, trisomy 13, or triploidy . Moreover, several patients and fetuses presenting myelomeningocele (MMC) and Xq27 duplications have been reported . Recently, the critical region was narrowed down to a 395‐kb segment that includes only the SOX3 gene, incriminating this genomic imbalance as a predisposing factor for NTDs .…”

Section: Introductionmentioning

confidence: 99%

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SOX3 duplication: A genetic cause to investigate in fetuses with neural tube defects

Hureaux¹,

Miled

Chatron

et al. 2019

Prenatal Diagnosis

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Objective: Neural tube defects (NTDs) are one of the most common congenital anomalies caused by a complex interaction of many genetic and environmental factors. In about 10% of cases, NTDs are associated with genetic syndromes or chromosomal anomalies. Among these, SOX3 duplication has been reported in some isolated cases. The phenotype associated with this microduplication is variable and includes myelomeningocele (MMC) in both sexes as well as hypopituitarism and cognitive impairment in males. In order to determine the prevalence of this anomaly in fetuses with MMC, a retrospective cohort of fetuses with MMC was analyzed by quantitative PCR (qPCR) targeting SOX3 locus. Methods:The detection of an SOX3 microduplication by chromosomal microarray analysis (CMA) in two female fetuses with MMC prompted us to analyze retrospectively by qPCR this gene in a cohort of 53 fetuses with MMC.Results: In addition to our two initial cases, one fetus harboring an Xq27.1q28 duplication that encompasses the SOX3 gene was detected.Conclusion: Our data demonstrate that SOX3 duplication is a genomic imbalance involved in the pathogenesis of NTDs. In addition, our survey highlights the importance of CMA testing in fetuses with NTDs to enable genetic counseling upstream of any considerations of in utero fetal surgery.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

SOX3 duplication: A genetic cause to investigate in fetuses with neural tube defects

Hureaux¹,

Miled

Chatron

et al. 2019

Prenatal Diagnosis

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“…9 The utilization of genomic microarray analysis has allowed researchers to identify the genes on Xq that are associated with these phenotypes when duplicated, including STAG2 (Xq25), SOX3 (Xq27.1), and MECP2 (Xq28). [10][11][12][13] However, many of the reported Xq duplications do not contain clearly causative genes, demonstrating the need to characterize additional patients with Xq duplications. In this study, we report 6 additional patients from 2 unrelated families with duplications involving the Xq25q26.2 region.…”

Section: Discussionmentioning

confidence: 99%

Delineating the Clinical Spectrum Associated With Xq25q26.2 Duplications: Report of 2 Families and Review of the Literature

et al. 2018

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To date, 13 patients with interstitial microduplications involving Xq25q26.2 have been reported. Here, we report 6 additional patients from 2 families with duplications involving Xq25q26.2. Family I carries a 5.3-Mb duplication involving 26 genes. This duplication was identified in 3 patients and was associated with microcephaly, growth failure, developmental delay, and dysmorphic features. Family II carries an overlapping 791-kb duplication that involves 3 genes. This duplication was identified in 3 patients and was associated with learning disability and speech delay. The size and gene content of published overlapping Xq25q26.2 duplications vary, making it difficult to define a critical region or establish a genotype-phenotype correlation. However, patients with overlapping duplications have been found to share common clinical features including microcephaly, growth failure, intellectual disability, learning difficulties, and dysmorphic features. The 2 families presented here provide additional insight into the phenotypic spectrum and clinical significance of duplications in this region.

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A SOX3 duplication and lumbosacral spina bifida in three generations

Butler

Fee

DuPont

et al. 2022

American J of Med Genetics Pt A

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Chromosomal aneuploidies, microduplications and microdeletions are the most common confirmed genetic causes of spina bifida. Microduplications of Xq27 containing the SOX3 gene have been reported in 11 cases, confirming the existence of an X‐chromosomal locus for spina bifida. A three generation kindred reported here with a SOX3 duplication has been identified in one of 17 kindreds with recurrences in the 29 years of the South Carolina Neural Tube Defect Prevention Program. Other recurrences during this time period included siblings with an APAF1 mutation, siblings with a CASP9 mutation, siblings with a microdeletion of 13q, and two sets of siblings with Meckel syndrome who did not have genetic/genomic studies performed.

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Duplication of SOX3 (Xq27) may be a risk factor for Neural Tube Defects

Cited by 11 publications

References 4 publications

SOX3 duplication: A genetic cause to investigate in fetuses with neural tube defects

SOX3 duplication: A genetic cause to investigate in fetuses with neural tube defects

Delineating the Clinical Spectrum Associated With Xq25q26.2 Duplications: Report of 2 Families and Review of the Literature

A SOX3 duplication and lumbosacral spina bifida in three generations

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