Severe Neurological Phenotype in a Girl with Xp22.31 Triplication

Polo-Antúnez, Antonio; Arroyo-Carrera, I

doi:10.1159/000475795

Cited by 5 publications

(3 citation statements)

References 15 publications

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“…In two male fetuses, the imbalances were inherited from the mothers. Polo-Antúnez et al described a severe neurological phenotype in a girl with Xp22.31 tetrasomy [ 38 ]. In contrast, we identified no abnormal findings in two females and a mother, all of whom had Xp22.31 tetrasomy.…”

Section: Discussionmentioning

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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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%

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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“…Xp22.31 duplications, the counterpart of the Xp22.31 deletion causing XLI containing the STS gene, are among the most frequent findings in genetic laboratories but are challenging to interpret [1, 5–8]. The unequal recombination flanking the STS region frequently produces the 1.6 Mb recurrent duplication contains four known genes, including HDHD1 , STS , VCX , and PNPLA4 [9]. At present, the research on Xp22.31 microdeletion has been relatively mature.…”

Section: Introductionmentioning

confidence: 99%

A prenatal diagnosis and genetics study of five pedigrees in the Chinese population with Xp22.31 microduplication

et al. 2019

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BackgroundCopy number variations (CNVs) can contribute to human phenotype, phenotypic diversity and disease susceptibility, while others may benign. In the current study, an attempt to investigate the pathogenicity of CNVs in chromosome Xp22.31 was explored.MethodsG-banding and SNP-array techniques were used to analyze chromosome karyotypes and CNVs in fetuses. Parents associate with five different pedigrees possessing high risk factors in pregnancy were considered with such parameters as advanced age, high risk of serological screening and ultrasound abnormalities.ResultsThe fetuses’ amniotic fluid karyotypes were 46, XX and those of their parents with the five pedigrees revealed no abnormalities. Here, we noticed a series of individuals with Xp22.31 duplications ranging from 534.6 kb to 1.6 Mb. It was detected through SNP array that the fetuses in Pedigree 1 and 2 had ~ 600 kb duplications in the Xp22.31 region of their X chromosomes which contained two OMIM genes, HDHD1 (OMIM: 306480) and part of STS (OMIM: 300747). The fetuses of Pedigrees 3, 4 and 5 had 1.6 Mb duplication in the same chromosome which contained four OMIM genes: HDHD1 (OMIM: 306480), STS (OMIM: 300747), PNPLA4 (OMIM: 300102) and VCX (OMIM: 300229). The duplications in the fetuses of Pedigrees 1 and 5 were inherited from the non-phenotypic parents. Pedigrees 3 and 4 refused to perform parental verification. Finally, four of the five pedigrees continue towards pregnancy with no abnormalities being observed during followed-ups.ConclusionOur study first showed duplications of Xp22.31 in Chinese population. Clinical and genetic investigation on five different pedigrees, we consider the duplication of these fragments as likely benign copy number variants (CNVs). We suggest that the duplications of Xp22.31 with recurrent duplication as a benign CNVs .

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“…The pathogenicity of Xp22.31 duplication seems to be controversial. Previous reports have shown that some individuals with duplication of this region had varied degrees of neurological impairment, including growth retardation, intellectual disability, autistic spectrum disorders, hypotonia, seizures, psychomotor retardation, and mild special face ( Faletra et al, 2012 ; Pavone et al, 2019 ; Polo-Antunez & Arroyo-Carrera, 2017 ). Some studies showed that duplication of Xp22.31 is a risk factor for abnormal phenotypes or benign variants ( Liu et al, 2011 ; Zhuang et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Combined use of karyotyping and copy number variation sequencing technology in prenatal diagnosis

Zhang

Lü

et al. 2022

PeerJ

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Background Karyotyping and genome copy number variation sequencing (CNV-seq) are two techniques frequently used in prenatal diagnosis. This study aimed to explore the diagnostic potential of using a combination of these two methods in order to provide a more accurate clinical basis for prenatal diagnosis. Methods We selected 822 pregnant women undergoing amniocentesis and separated them into six groups according to different risk indicators. Karyotyping and CNV-seq were performed simultaneously to compare the diagnostic performance of the two methods. Results Among the different amniocentesis indicators, abnormal fetal ultrasounds accounted for 39.29% of the total number of examinees and made up the largest group. The abnormal detection rate of non-invasive prenatal testing (NIPT) high risk was 37.93% and significantly higher than the other five groups (P < 0.05). The abnormal detection rate of mixed indicators was significantly higher than the history of the adverse reproductive outcomes group (P = 0.0151). The two methods combined found a total of 119 abnormal cases (14.48%). Karyotyping detected 57 cases (6.93%) of abnormal karyotypes, 30 numerical aberrations, and 27 structural aberrations. CNV-seq identified 99 cases (12.04%) with altered CNVs, 30 cases of chromosome aneuploidies, and 69 structural aberrations (28 pathogenic, eight that were likely pathogenic, and 33 microdeletion/duplication variants of uncertain significance (VUS)). Thirty-seven cases were found abnormal by both methods, 20 cases were detected abnormally by karyotyping (mainly mutual translocation and mostly balanced), and 62 cases of microdeletion/duplication were detected by CNV-seq. Steroid sulfatase gene (STS) deletion was identified at chromosome Xp22.31 in three cases. Postnatal follow-up confirmed that babies manifested skin abnormalities one week after birth. Six fetuses had Xp22.31 duplications ranging from 1.5 Kb to 1.7 Mb that were detected by CNV-seq. Follow-up showed that five babies presented no abnormalities during follow-up, except for one terminated pregnancy due to a history of adverse reproductive outcomes. Conclusion The combination of using CNV-seq and karyotyping significantly improved the detection rate of fetal pathogenic chromosomal abnormalities. CNV-seq is an effective complement to karyotyping and improves the accuracy of prenatal diagnosis.

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Severe Neurological Phenotype in a Girl with Xp22.31 Triplication

Cited by 5 publications

References 15 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

A prenatal diagnosis and genetics study of five pedigrees in the Chinese population with Xp22.31 microduplication

Combined use of karyotyping and copy number variation sequencing technology in prenatal diagnosis

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