Subterminal deletion/duplication event in an affected male due to maternal X chromosome pericentric inversion

Kokalj-Vokac, Nadja; Marcun-Varda, Natasa; Zagorac, Andreja; Erjavec-Škerget, Alenka; Zagradišnik, Boris; Todorovic, Mirjana; Gregorič, Alojz

doi:10.1007/s00431-004-1519-5

Cited by 10 publications

(15 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, at least five patients (Table IB) are reported in the literature with gross rearrangements involving Xp22, who did not present with features of CDPX1 despite a proven deletion of ARSE [de Vries et al, 1999; Seidel et al, 2001; Boycott et al, 2003; Kokalj‐Vokac et al, 2004]. In these cases deletion of ARSE was an incidental finding on cytogenetic analysis, which was performed because the complex phenotype of the patients was suggestive of a genomic alteration.…”

Section: Discussionmentioning

confidence: 99%

X‐linked brachytelephalangic chondrodysplasia punctata: A simple trait that is not so simple

Casarin

Rusalen

Doimo

et al. 2009

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Brachytelephalangic chondrodysplasia punctata (CDPX1) is an X-linked recessive disorder caused by mutations in the arylsulfatase E (ARSE) gene, characterized by the presence of stippled epiphyses on radiograms in infancy and early childhood. Other features include hypoplasia of the midface and of the nasal bone, short stature, brachytelephalangy, and ectopic calcifications. Patients display marked clinical variability and there is no clear genotype-phenotype correlation. We report on a 14-month-old boy who presented with respiratory stridor due to tracheal calcifications. He had mild midface hypoplasia and brachytelephalangy, but lacked other features of CDPX1, such as short stature and epiphyseal stippling. Analysis of ARSE detected a deletion involving exons 7-10. His maternal grandfather harbored the same defect but lacked any clinical manifestation. These findings underscore two important points. First, the absence of stippled epiphyses on radiograms should not be considered an exclusion criteria for ARSE mutation screening in patients with other features of the disease, especially after the neonatal period. Second, counseling to parents of affected children should be cautious because although the theoretical risk of inheriting the ARSE mutation is 50% for every male child of a carrier mother, it is not possible to determine whether he will develop features of CDPX1 and the eventual severity of symptoms. The actual risk of developing the disease is probably lower than 50%. Conversely, normal prenatal sonography does not rule out potentially severe complications such as tracheal stenosis.

show abstract

Section: Discussionmentioning

confidence: 99%

X‐linked brachytelephalangic chondrodysplasia punctata: A simple trait that is not so simple

Casarin

Rusalen

Doimo

et al. 2009

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…These cases are presumed to be the result of either a recombination event in a parent carrying a pericentric inversion [23][24][25][26][27] or inherited from a phenotypically normal mother carrying the abnormal X. 28 We report two additional cases in which an Xq duplication encompassing MECP2 was accompanied by an Xp deletion, resulting from a specific intrachromosomal rearrangement in which the duplicated segment of Xq was translocated to the Xp22.3 band.…”

Section: Xp-xq Rearrangementsmentioning

confidence: 99%

“…The pregnancy was complicated by influenza associated with dehydration. Literature (n¼5) [21][22][23] Literature (n¼8) [25][26][27][28] …”

Section: Casementioning

confidence: 99%

MECP2 duplications in six patients with complex sex chromosome rearrangements

et al. 2010

View full text Add to dashboard Cite

Duplications of the Xq28 chromosome region resulting in functional disomy are associated with a distinct clinical phenotype characterized by infantile hypotonia, severe developmental delay, progressive neurological impairment, absent speech, and proneness to infections. Increased expression of the dosage-sensitive MECP2 gene is considered responsible for the severe neurological impairments observed in affected individuals. Although cytogenetically visible duplications of Xq28 are well documented in the published literature, recent advances using array comparative genomic hybridization (CGH) led to the detection of an increasing number of microduplications spanning MECP2. In rare cases, duplication results from intrachromosomal rearrangement between the X and Y chromosomes. We report six cases with sex chromosome rearrangements involving duplication of MECP2. Cases 1-4 are unbalanced rearrangements between X and Y, resulting in MECP2 duplication. The additional Xq material was translocated to Yp in three cases (cases 1-3), and to the heterochromatic region of Yq12 in one case (case 4). Cases 5 and 6 were identified by array CGH to have a loss in copy number at Xp and a gain in copy number at Xq28 involving the MECP2 gene. In both cases, fluorescent in situ hybridization (FISH) analysis revealed a recombinant X chromosome containing the duplicated material from Xq28 on Xp, resulting from a maternal pericentric inversion. These cases add to a growing number of MECP2 duplications that have been detected by array CGH, while demonstrating the value of confirmatory chromosome and FISH studies for the localization of the duplicated material and the identification of complex rearrangements.

show abstract

“…When the breakpoints are flanked by repeated sequences, an intramolecular recombination between them could occur during spermatogenesis [22]. Otherwise, the rearrangement could be generated by a recombination event between an X chromosome with a pericentric inversion and the normal homolog during female meiosis [6, 23]. In this family, we defined the breakpoints through FISH and array-CGH analyses and homologous repeated sequences were not present in these regions, making the pericentric inversion the most likely promoting mechanism.…”

Section: Discussionmentioning

confidence: 99%

Cytogenetic and molecular characterization of a recombinant X chromosome in a family with a severe neurologic phenotype and macular degeneration

et al. 2015

View full text Add to dashboard Cite

BackgroundDuplications of MECP2 gene in males cause a syndrome characterized by distinctive clinical features, including severe to profound mental retardation, infantile hypotonia, mild dysmorphic features, poor speech development, autistic features, seizures, progressive spasticity and recurrent infections. Patients with complex chromosome rearrangements, leading to Xq28 duplication, share most of the clinical features of individuals with tandem duplications, in particular neurologic problems, suggesting a major pathogenetic role of MECP2 overexpression.ResultsWe performed cytogenetic and molecular cytogenetic studies in a previously described family with affected males showing congenital ataxia, late-onset progressive myoclonic encephalopathy and selective macular degeneration. Microsatellite, FISH and array-CGH analyses identified a recombinant X chromosome with a deletion of the PAR1 region, encompassing SHOX, replaced by a duplicated segment of the Xq28 terminal portion, including MECP2.ConclusionsOur report describes the identification of the actual genetic cause underlying a severe syndrome that previous preliminary analyses erroneously associated to a terminal Xp22.33 region. In the present family as well as in previously reported patients with similar rearrangements, the observed neurologic phenotype is ascribable to MECP2 duplication, with an undefined contribution of the other involved genes. Maculopathy, presented by affected males reported here, could be a novel clinical feature associated to Xq28 disomy due to recombinant X chromosomes, but at present the underlying pathogenetic mechanism is unknown and this potential clinical correlation should be confirmed through the collection of additional patients.

show abstract

Subterminal deletion/duplication event in an affected male due to maternal X chromosome pericentric inversion

Abstract: Fluorescent in situ hybridisation techniques using subtelomeric DNA probes are essential tools for detection of such complex submicroscopic chromosomal rearrangements as the dup/del event of the X chromosome described in our patient.

Cited by 10 publications

References 18 publications

X‐linked brachytelephalangic chondrodysplasia punctata: A simple trait that is not so simple

X‐linked brachytelephalangic chondrodysplasia punctata: A simple trait that is not so simple

MECP2 duplications in six patients with complex sex chromosome rearrangements

Cytogenetic and molecular characterization of a recombinant X chromosome in a family with a severe neurologic phenotype and macular degeneration

Contact Info

Product

Resources

About