The contribution of Xp22.31 gene dosage to Turner and Klinefelter syndromes and sex-biased phenotypes

Davies, William

doi:10.1016/j.ejmg.2021.104169

Cited by 7 publications

(8 citation statements)

References 168 publications

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“…This seems to explain the asymptomatic nature of females with Xp22.31 deletion in our study. Large cohort studies have demonstrated that the phenotypic differences between female Xp22.31 deletion carriers and non-carriers are negligible [ 2 , 5 ]. Thus, the interpretation of female carriers is not controversial in prenatal diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…Female deletion carriers have been reported to have a clinical phenotype of benign corneal opacities [ 4 ]. Recent studies have shown that the overall health and reproduction of heterozygous female carriers for Xp22.31 deletion exhibit apparently no or negligible differences compared to those of female non-carriers [ 2 , 5 ]. Thus, the interpretation of female carriers is not controversial in prenatal diagnosis.…”

Section: Introductionmentioning

confidence: 99%

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Xp22.31 copy number variations in 87 fetuses: refined genotype–phenotype correlations by prenatal and postnatal follow-up

Huang

Hou

et al. 2023

BMC Med Genomics

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Background Xp22.31 deletion and duplication have been described in various studies, but different laboratories interpret pathogenicity differently. Objectives Our study aimed to refine the genotype–phenotype associations between Xp22.31 copy number variants in fetuses, with the aim of providing data support to genetic counseling. Methods We retrospectively analyzed karyotyping and single nucleotide polymorphism array results from 87 fetuses and their family members. Phenotypic data were obtained through follow-up visits. Results The percentage of fetuses carrying the Xp22.31 deletions (9 females, 12 males) was 24.1% (n = 21), while duplications (38 females, 28 males) accounted for 75.9% (n = 66). Here, we noted that the typical region (from 6.4 to 8.1 Mb, hg19) was detected in the highest ratio, either in the fetuses with deletions (76.2%, 16 of 21) or duplications (69.7%, 46 of 66). In female deletion carriers, termination of pregnancy was chosen for two fetuses, and the remaining seven were born without distinct phenotypic abnormalities. In male deletion carriers, termination of pregnancy was chosen for four fetuses, and the remaining eight of them displayed ichthyosis without neurodevelopmental anomalies. In two of these cases, the chromosomal imbalance was inherited from the maternal grandfathers, who also only had ichthyosis phenotypes. Among the 66 duplication carriers, two cases were lost at follow-up, and pregnancy was terminated for eight cases. There were no other clinical findings in the rest of the 56 fetuses, including two with Xp22.31 tetrasomy, for either male or female carriers. Conclusion Our observations provide support for genetic counseling in male and female carriers of Xp22.31 copy number variants. Most of them are asymptomatic in male deletion carriers, except for skin findings. Our study is consistent with the view that the Xp22.31 duplication may be a benign variant in both sexes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Xp22.31 copy number variations in 87 fetuses: refined genotype–phenotype correlations by prenatal and postnatal follow-up

Huang

Hou

et al. 2023

BMC Med Genomics

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“…In the XCIE, the peak genes in 47XXY are similar to those in 46XX, while the CG genes are similar to those in 46XY. Previous study suggested that a lower Xp22.31 gene dosage in 47XXY males may increase their likelihood of exhibiting particular phenotypes relative to females (Davies, 2021). The unbalanced CG and peak calling may give an explanation for the increased prevalence in 47XXY of several conditions, which are Frontiers in Molecular Biosciences frontiersin.org usually more common in women (gynoid proportions and autoimmune diseases) (Zitzmann et al, 2004).…”

Section: Discussionmentioning

confidence: 98%

Integrative epigenome profiling of 47XXY provides insights into whole genomic DNA hypermethylation and active chromatin accessibility

Miao

Zeng

Lee

et al. 2023

Front. Mol. Biosci.

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Klinefelter syndrome (KS, 47XXY) is a disorder characterized by sex chromosomal aneuploidy, which may lead to changes in epigenetic regulations of gene expression. To define epigenetic architectures in 47XXY, we annotated DNA methylation in euploid males (46XY) and females (46XX), and 47XXY individuals using whole genome bisulfite sequencing (WGBS) and integrated chromatin accessbilty, and detected abnormal hypermethylation in 47XXY. Furthermore, we detected altered chromatin accessibility in 47XXY, in particular in chromosome X, using Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) in cultured amniotic cells. Our results construct the whole genome-wide DNA methylation map in 47XXY, and provide new insights into the early epigenomic dysregulation resulting from an extra chromosome X in 47XXY.

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“…Contiguous gene deletion syndrome at Xp22.3 resulting in nullisomy in males or Turner syndrome patients is characterized by the combination of one or more monogenic disorders and clinical findings as short stature (short stature homeobox gene, SHOX ), chondrodysplasia punctata (arylsulfatase genes - ARSD , ARSE , ARSF ), X-linked ichthyosis (arylsulfatase C or steroid sulfatase gene, STS ), ocular albinism type I ( OA1 ) and elements of X-linked neurodevelopmental disorders and Kallmann syndrome ( KAL1 ; reduced hypothalamic and pituitary function with resulting hypogonadotropic hypogonadism and hypoplasia of the olfactory bulb) [ 1 ], whereas the term Rud’s syndrome should no longer be used [ 2 ]. FG syndrome 3 is also mapped to this region [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Hypertrophic pyloric stenosis masked by kidney failure in a male infant with a contiguous gene deletion syndrome at Xp22.31 involving the steroid sulfatase gene: case report

Schierz¹,

Giuffrè²,

Cimador³

et al. 2022

Ital J Pediatr

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Background Contiguous gene deletion syndrome at Xp22.3 resulting in nullisomy in males or Turner syndrome patients typically encompasses the steroid sulfatase gene (STS) and contiguously located other genes expanding the phenotype. In large deletions, that encompass also the Kallmann syndrome 1 gene (KAL1), occasionally infantile hypertrophic pyloric stenosis (IHPS) and congenital anomalies of the kidney and urinary tract (CAKUT) have been reported. Patient presentation We report on a male newborn with family history in maternal uncle of renal abnormalities and short stature still without ichthyosiform dermatosis. The baby presented CAKUT with kidney failure and progressive vomiting. Renal bicarbonate loss masked hypochloremic and hypokalemic metabolic alkalosis classically present in IHPS and delayed its diagnosis. Antropyloric ultrasound examination and cystourethrography were diagnostic. After Fredet-Ramstedt extramucosal pyloromyotomy feeding and growing was regular and he was discharged home. Comparative whole-genome hybridization detected a maternal inherited interstitial deletion of 1.56 Mb on Xp22.31(6,552,712_8,115,153) × 0 involving the STS gene, but not the KAL1 gene. Conclusions Aberrant cholesterol sulfate storage due to STS deletion as the underlying pathomechanism is not limited to oculocutaneous phenotypes but could also lead to co-occurrence of both IHPS and kidney abnormalities, as we report. Thus, although these two latter pathologies have a high incidence in the neonatal age, their simultaneous association in our patient is resembling not a chance but a real correlation expanding the clinical spectrum associated with Xp22.31 deletions.

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The contribution of Xp22.31 gene dosage to Turner and Klinefelter syndromes and sex-biased phenotypes

Cited by 7 publications

References 168 publications

Xp22.31 copy number variations in 87 fetuses: refined genotype–phenotype correlations by prenatal and postnatal follow-up

Xp22.31 copy number variations in 87 fetuses: refined genotype–phenotype correlations by prenatal and postnatal follow-up

Integrative epigenome profiling of 47XXY provides insights into whole genomic DNA hypermethylation and active chromatin accessibility

Hypertrophic pyloric stenosis masked by kidney failure in a male infant with a contiguous gene deletion syndrome at Xp22.31 involving the steroid sulfatase gene: case report

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