Does the 1.5 Mb microduplication in chromosome band <i>Xp22.31</i> have a pathogenetic role? New contribution and a review of the literature

Faletra, Flavio; D’Adamo, Pio; Rocca, Maria Santa; Carrozzi, Marco; Perrone, Maria Dolores; Pecile, Vanna; Gasparini, Paolo

doi:10.1002/ajmg.a.34398

Cited by 19 publications

(30 citation statements)

References 14 publications

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“…This girl has IDs but she did not have the typical facial characteristics associated with Wolf-Hirschhorn syndrome. Patient 43 contained a duplication of ~1.6 Mb in Xp22.31, as reported in another patient by Faletra et al (2012). Similarly, variants were observed both in normal individuals and in individuals with clinical conditions associated with ID.…”

Section: Discussionsupporting

confidence: 54%

Array-CGH analysis in patients with intellectual disability and/or congenital malformations in Brazil

et al. 2016

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ABSTRACT. In several patients, intellectual disability and/or congenital malformation may be attributed to chromosomal changes. In this study, we conducted an array-CGH test of 200 patients from the Northeast of Brazil with intellectual disability and/or congenital malformation. Blood samples were collected from the proband and from their parents when possible. DNA was extracted and investigated using the array-CGH test. Findings were evaluated for the pathogenicity in databases of benign and pathogenic changes (ISCA, UCSC, DGV, and DECIPHER). Forty-seven copy number variations (CNVs) were identified in 43/200 (21.5%) patients, including 25/98 (25.5%) in males and 22/102 (21.57%) in females. We considered 33 of these to be clinically significant, reaching a diagnosis rate of 16.5%. The sizes of the CNVs varied from 102 kb to 24 Mb in deletions and from 115 kb to 140 Mb in duplications. In 10/47 (21.3%) patients, the rearrangement involved a sex chromosome. Thirty-nine patients had one chromosomal aberration, while 2 concomitant abnormalities were detected in 4 patients. Ten of 47 CNVs (21.3%) were > 5Mb in size. Fifteen patients had CNVs related to known syndromes. This research highlights the contribution of submicroscopic chromosomal changes to the etiology of intellectual disability and/or congenital malformation, particularly the implication of chromosomal abnormalities detected using an array-CGH test, with a high rate of 16.5%. Thus, our results support the use of array-CGH replacing standard karyotype as the first-tier cytogenetic diagnostic test for patients with multiple congenital anomalies and/or intellectual disability.

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Section: Discussionsupporting

confidence: 54%

Array-CGH analysis in patients with intellectual disability and/or congenital malformations in Brazil

et al. 2016

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“…Regarding the gender of the reported cases, except Furrow et al [2011], who reported only males, the studies of Li et al [2010], Liu et al [2011], and Faletra et al [2012] identified both males and females with no significant gender differences.…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…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.…”

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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.…”

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confidence: 99%

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Severe Neurological Phenotype in a Girl with Xp22.31 Triplication

Polo-Antúnez¹,

Arroyo-Carrera

2017

Mol Syndromol

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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.

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Nine patients with Xp22.31 microduplication, cognitive deficits, seizures, and talipes anomalies

Slavotinek

Novelli

et al. 2014

American J of Med Genetics Pt A

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Comparative genomic hybridization (CGH) arrays have significantly changed the approach to identifying genetic alterations causing intellectual disability and congenital anomalies. Several studies have described the microduplication of Xp22.31, involving the STS gene. In such reports characteristic features and pathogenicity of Xp22.31 duplications remains a subject of debate. Here we present a series of nine previously unreported individuals with Xp22.31 duplications, found through microarray analysis in the course of genetic workup for developmental delay, associated with a combination of talipes anomalies, seizures and/or feeding difficulties. The size of the Xp22.31 duplications ranged from 294 kb to 1.6 Mb. We show a comparison of the breakpoints, inheritance and clinical phenotype, and a review of the literature. This clinically detailed series of Xp22.31 duplication patients provides evidence that the Xp22.31 duplication contributes to a common phenotype.

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Does the 1.5 Mb microduplication in chromosome band Xp22.31 have a pathogenetic role? New contribution and a review of the literature

Cited by 19 publications

References 14 publications

Array-CGH analysis in patients with intellectual disability and/or congenital malformations in Brazil

Array-CGH analysis in patients with intellectual disability and/or congenital malformations in Brazil

Severe Neurological Phenotype in a Girl with Xp22.31 Triplication

Nine patients with Xp22.31 microduplication, cognitive deficits, seizures, and talipes anomalies

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