Interstitial microduplication of Xp22.31: Causative of intellectual disability or benign copy number variant?

Li, Feng; Shen, Yiping; Köhler, U; Sharkey, Freddie H.; Menon, Deepa; Coulleaux, Laurence; Malan, Valérie; Rio, Marlène; McMullan, Dominic; Cox, Helen; Fagan, Kerry; Gaunt, Lorraine; Metcalfe, Kay; Heinrich, Uwe; Hislop, Gordon; Maye, Una; Sutcliffe, Maxine J.; Wu, Bai Lin; Thiel, Brian D.; Mulchandani, Surabhi; Conlin, Laura K.; Spinner, Nancy B.; Murphy, Kathleen M.; Batista, Denise

doi:10.1016/j.ejmg.2010.01.004

Cited by 64 publications

(76 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Currently, there is a debate about the pathogenicity of the Xp22.31 duplication [Li et al, 2010;Furrow et Liu et al, 2011;Faletra et al, 2012;Esplin et al, 2014]. An increasing number of patients with the duplication share a common neurobehavioral phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…laboratories but are challenging to interpret [Shaffer et al, 2007;Li et al, 2010;Furrow et al, 2011;Liu et al, 2011;Faletra et al, 2012;Esplin et al, 2014]. This recurrent duplication contains 4 known genes, PUDP , STS , VCX , and PNPLA4 as well as 2 microRNAs, MIR651 and MIR4767.…”

mentioning

confidence: 99%

“…There is a high incidence of this duplication in clinical cases referred for array comparative genomic hybridization (aCGH) and ascertained due to neurobehavioral abnormalities, but the duplication is also observed in the general population. In the majority of clinical cases, it is inherited from a parent, most of them clinically unaffected [Li et al, 2010;Furrow et al, 2011;Liu et al, 2011;Faletra et al, 2012;Esplin et al, 2014]. The duplication may predispose to disease, but the manifestation may require additional genetic and/or environmental factors.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Severe Neurological Phenotype in a Girl with Xp22.31 Triplication

Polo-Antúnez¹,

Arroyo-Carrera

2017

Mol Syndromol

View full text Add to dashboard Cite

The Xp22.31 duplication is a copy number variant which is challenging to categorize as pathogenic or benign. There is an increasing number of patients with the duplication and a neurobehavioral phenotype, but the duplication is almost always inherited from a parent, who in some cases is phenotypically normal. Also, the duplication is detected in the general population, though in a smaller percentage than in clinically ascertained populations. The Xp22.31 triplication has only been identified in 3 individuals of a large cohort of developmental delay cases but never in the control cohorts or general population. We report a severely affected female with an Xp22.31 tetrasomy, inherited from duplications identified in both phenotypically normal parents. Although our study has limitations, it suggests that the Xp22.31 triplication seems to be more penetrant than the duplication and is associated with a neurological phenotype.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Severe Neurological Phenotype in a Girl with Xp22.31 Triplication

Polo-Antúnez¹,

Arroyo-Carrera

2017

Mol Syndromol

View full text Add to dashboard Cite

show abstract

“…In these cases, the rearrangements occurred in one of the X chromosomes, probably not resulting in complete functional disomy due to X inactivation. In a collaborative study, Li et al [2010] reported 15 male and 14 female patients with in-tandem interstitial Xp22.31 duplications varying in size between 149 kb and 1.74 Mb. These duplications were found at a higher frequency in individuals with abnormal phenotypes, especially males, because their only X chromosome is abnormal and active, resulting in Xp disomy.…”

Section: Discussionmentioning

confidence: 99%

“…Among the few reported cases, there is a family with 2 male and 2 female patients with a duplication Xp22pter who presented intellectual disability and other phenotypic findings [Melaragno et al, 1998], and a patient with Xp21.2pter duplication with mild phenotypic anomalies, developmental delay, and seizures [Gustashaw et al, 1994]. Besides larger duplications, submicroscopic Xp22.31 duplications have been reported as a possible cause of intellectual disability and/or developmental delay [Mencarelli et al, 2008;Li et al, 2010;Olson et al, 2014].…”

mentioning

confidence: 99%

Wolf-Hirschhorn Syndrome with Epibulbar Dermoid: An Unusual Association in a Patient with 4p Deletion and Functional Xp Disomy

Bragagnolo

Colovati

Guilherme

et al. 2016

Cytogenet Genome Res

View full text Add to dashboard Cite

Wolf-Hirschhorn syndrome (WHS) is a contiguous gene and multiple malformation syndrome that results from a deletion in the 4p16.3 region. We describe here a 6-month-old girl that presented with WHS features but also displayed unusual findings, such as epibulbar dermoid in the left eye, ear tags, and left microtia. Although on G-banding her karyotype appeared to be normal, chromosomal microarray analysis revealed an ∼13-Mb 4p16.3p15.33 deletion and an ∼9-Mb Xp22.33p22.31 duplication, resulting from a balanced maternal t(X;4)(p22.31;p15.33) translocation. The patient presented with functional Xp disomy due to an unbalanced X-autosome translocation, a rare cytogenetic finding in females with unbalanced rearrangements. Sequencing of both chromosome breakpoints detected no gene disruption. To the best of our knowledge, this is the first patient described in the literature with WHS and epibulbar dermoid, a typical characteristic of the oculoauriculovertebral spectrum (OAVS). Our data suggest that possible candidate genes for OAVS may have been deleted along with the WHS critical region.

show abstract

Duplication of the STS region in males is a benign copy‐number variant

Furrow

Theisen

Velsher

et al. 2011

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Copy-number variants (CNVs) are a common finding in the human genome, with copy gains occurring at a higher frequency than losses in several databases of genomic variants in normal individuals. Copy gains of the steroid sulfatase (STS) gene have been seen in both males and females. Although deletion of STS in males is known to cause X-linked ichthyosis, the clinical significance of STS copy gains is less clear, with the duplication reported in individuals with abnormal phenotypes and normal relatives. We identified 72 males submitted to our laboratory for microarray-based comparative genomic hybridization with duplications in the STS region (chrX:6,465,812-8,093,195). In 40 (56%) patients, maternal blood was available, and the duplication was found to be inherited from the patient's apparently phenotypically normal mother in each of the 40 patients. We also identified three females who inherited a duplication of the STS region from phenotypically normal fathers, and a phenotypically normal uncle who had the same duplication as his nephews. In the remaining cases the inheritance could not be confirmed owing to lack of parental samples available for testing. Of the 72 subjects, 10 (14%) had an additional CNV elsewhere in the genome known to be clinically significant and likely causative of the patient's presenting symptoms. Based on the frequency with which duplications have been identified in clinically normal and abnormal individuals, we suggest a gain of STS in males is a population variant and unlikely to be clinically significant.

show abstract

Interstitial microduplication of Xp22.31: Causative of intellectual disability or benign copy number variant?

Cited by 64 publications

References 37 publications

Severe Neurological Phenotype in a Girl with Xp22.31 Triplication

Severe Neurological Phenotype in a Girl with Xp22.31 Triplication

Wolf-Hirschhorn Syndrome with Epibulbar Dermoid: An Unusual Association in a Patient with 4p Deletion and Functional Xp Disomy

Duplication of the STS region in males is a benign copy‐number variant

Contact Info

Product

Resources

About