Epilepsy phenotype in patients with Xp22.31 microduplication

Brinciotti, M.; Fioriello, Francesca; Mittica, A.; Bernardini, Laura; Goldoni, Marina; Matricardi, M.

doi:10.1016/j.ebcr.2018.10.004

Cited by 3 publications

(1 citation statement)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the segment detected in Family 3 overlapped what was discussed in the study, the woman (F3-II-3) chose TOP in her first pregnancy. However, further published literature noted that similar Xp22.31 duplications recurred in some families in not only phenotypically abnormal but also normal individuals [ 8 , 9 , 17 ]. As a result, the Xp22.31 duplication may be simply a benign CNV or a predisposing factor (i.e., a high-risk locus).…”

Section: Discussionmentioning

confidence: 99%

Relevance of Copy Number Variation at Chromosome X in Male Fetuses Inherited from the Mother May Be Ascertained by Including Male Relatives from the Maternal Lineage in Addition to Trio Analyses

Chen

Lee

et al. 2020

Genes

View full text Add to dashboard Cite

Chromosome microarray analysis has been used for prenatal detection of copy number variations (CNVs) and genetic counseling of CNVs has been greatly improved after the accumulation of knowledge from postnatal outcomes in terms of the genotype-phenotype correlation. However, a significant number of CNVs are still regarded as variants of unknown significance (VUS). CNVs at the chromosome X (X-CNVs) represent a unique group of genetic changes in genetic counseling; X-CNVs are similar to X-linked recessive monogenic disorders in that the prognosis in males is expected to be poor. Trio analysis is typically advised to patients with X-CNVs but such an approach may be inadequate in prenatal settings since the clinical relevance is sometimes uninformative, particularly for the maternally inherited X-CNVs in male fetuses. Here, we reported four healthy women whose male fetuses were found to have X-CNVs inherited from the mothers. The X-CNVs were initially recognized as VUS or likely pathogenic in males according to the publicly available information. After extending genetic analyses to male relatives of the maternal lineages, however, the relevance of the X-CNVs was reconsidered to be likely benign. The results highlight that an extended analysis to include more relatives, in addition to the parents, provides further information for genetic counseling when X-CNVs are encountered in prenatal settings.

show abstract

Section: Discussionmentioning

confidence: 99%

Relevance of Copy Number Variation at Chromosome X in Male Fetuses Inherited from the Mother May Be Ascertained by Including Male Relatives from the Maternal Lineage in Addition to Trio Analyses

Chen

Lee

et al. 2020

Genes

View full text Add to dashboard Cite

show abstract

Medical and neurobehavioural phenotypes in male and female carriers of Xp22.31 duplications in the UK Biobank

Gubb

Brcic

Underwood

et al. 2020

Human Molecular Genetics

View full text Add to dashboard Cite

Deletions spanning the STS (steroid sulfatase) gene at Xp22.31 are associated with X-linked ichthyosis, corneal opacities, testicular maldescent, cardiac arrhythmia, and higher rates of developmental and mood disorders/traits, possibly related to the smaller volume of some basal ganglia structures. The consequences of duplication of the same genomic region have not been systematically assessed in large or adult samples, although evidence from case reports/series has indicated high rates of developmental phenotypes. We compared multiple measures of physical and mental health, cognition and neuroanatomy in male (n = 414) and female (n = 938) carriers of 0.8–2.5 Mb duplications spanning STS, and non-carrier male (n = 192, 826) and female (n = 227, 235) controls from the UK Biobank (recruited aged 40–69 from the UK general population). Clinical and self-reported diagnoses indicated a higher prevalence of inguinal hernia and mania/bipolar disorder respectively in male duplication carriers, and a higher prevalence of gastro-oesophageal reflux disease and blistering/desquamating skin disorder respectively in female duplication carriers; duplication carriers also exhibited reductions in several depression-related measures, and greater happiness. Cognitive function and academic achievement did not differ between comparison groups. Neuroanatomical analysis suggested greater lateral ventricle and putamen volume in duplication carriers. In conclusion, Xp22.31 duplications appear largely benign, but could slightly increase the likelihood of specific phenotypes (although results were only nominally-significant). In contrast to deletions, duplications might protect against depressive symptoms, possibly via higher STS expression/activity (resulting in elevated endogenous free steroid levels), and through contributing towards an enlarged putamen volume. These results should enable better genetic counselling of individuals with Xp22.31 microduplications.

show abstract

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

View full text Add to dashboard Cite

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.

show abstract

Epilepsy phenotype in patients with Xp22.31 microduplication

Cited by 3 publications

References 21 publications

Relevance of Copy Number Variation at Chromosome X in Male Fetuses Inherited from the Mother May Be Ascertained by Including Male Relatives from the Maternal Lineage in Addition to Trio Analyses

Relevance of Copy Number Variation at Chromosome X in Male Fetuses Inherited from the Mother May Be Ascertained by Including Male Relatives from the Maternal Lineage in Addition to Trio Analyses

Medical and neurobehavioural phenotypes in male and female carriers of Xp22.31 duplications in the UK Biobank

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

Contact Info

Product

Resources

About