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

Abstract

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 .

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

“…Hence, duplications could potentially have dissociable effects on depressive and manic traits, acting to reduce the former whilst eliciting the latter. In terms of neuroanatomy, duplication carriers also exhibited evidence for enlarged left lateral ventricle volume relative to controls; this finding aligns with a previous observation of a widened left lateral ventricle in a fetus possessing an Xp22.31 1.6 Mb microduplication ( 21 ).…”

“…Case series/studies documenting predominantly young, clinically-ascertained, individuals with Xp22.31 duplications report a number of neurological features including intellectual disability/cognitive impairment (40%), autism or autistic behaviours (10–20%), global developmental delay (10%), delayed speech and language (10%) and seizures (10%), as well as other less common clinical manifestations including microcephaly (5–10%), muscular hypotonia (5–10%) and clinodactyly or shortness of the fifth finger (5%) ( 10–20 ), and ( Supplementary Material, Table 1 ). Whether the Xp22.31 duplication is pathogenic (particularly with regard to its role in brain function and head/facial dysmorphism), or whether it is benign but tends to occur in combination with other pathogenic mechanisms, has been a matter for debate ( 21–23 ).…”

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

“…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 ). In this study, we found that five babies with Xp22.31 duplication did not present with phenotypes during follow-up.…”

A de novo PAK1 likely pathogenic variant and a de novo terminal 1q microdeletion in a Chinese girl with global developmental delay, severe intellectual disability, and seizures

“…Approximately 2–3 ml peripheral blood were collected from the patient and the parents for karyotype analysis. The peripheral blood lymphocytes were harvested using a SinochromeChromprepII automatic chromosome harvesting system according to the standard protocol (Shanghai Lechen Biotechnology Co., Ltd.), which has been described previously in our study [ 13 ]. After staining with Giemsa stain, twenty karyotypes were counted and analyzed five karyotypes.…”