scholarly journals The int22h1/int22h2-Mediated Xq28 Duplication Syndrome: An Intersection between Neurodevelopment, Immunology, and Cancer

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 860
Author(s):  
Rami A. Ballout ◽  
Ayman W. El-Hattab

The int22h1/int22h2-mediated Xq28 duplication syndrome is a rare X-linked intellectual disability syndrome (XLIDS) arising from a duplication of the segment between intron 22 homologous regions 1 and 2, on the q28 subregion of the X chromosome. The main clinical features of the syndrome include intellectual disability, neurobehavioral abnormalities, and dysmorphic facial features. Due to the X-linked nature of the syndrome, affected males exhibit more severe phenotypes compared with heterozygous females. A unique distinguishing feature of the syndrome across the sexes, however, is a peculiar combination of recurrent sinopulmonary infections and atopy exclusively seen in a subset of affected males. In addition to the ‘typical’ 0.5 Mb duplication detected in most cases reported to date with the syndrome, a shortened centromeric version, and another 0.2 Mb telomerically shifted one, have been recently identified, with most detected duplications being maternally inherited, except for three recent cases found to have de novo duplications. Interestingly, a recently reported case of an affected male suggests a possible association of the syndrome with multiple malignancies, an observation that has been recently replicated in two pediatric patients. As a result, a better understanding of the pathogenesis of int22h1/int22h2-mediated Xq28 duplication syndrome may grant us a better understanding of the sex-specific differences in immunological responses, as well as the potential role of the genes involved by the duplication, in oncogenesis.

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 511
Author(s):  
Roberta Milone ◽  
Roberta Scalise ◽  
Rosa Pasquariello ◽  
Stefano Berloffa ◽  
Ivana Ricca ◽  
...  

Syndromic intellectual disability often obtains a genetic diagnosis due to the combination of first and next generation sequencing techniques, although their interpretation may require revaluation over the years. Here we report on a composite neuropsychiatric case whose phenotype includes moderate intellectual disability, spastic paraparesis, movement disorder, and bipolar disorder, harboring a 1.802 Mb de novo 1q21.3q22 duplication. The role of this duplication has been reconsidered in the light of negativity of many other genetic exams, and of the possible pathogenic role of many genes included in this duplication, potentially configuring a contiguous gene-duplication syndrome.


2021 ◽  
pp. mcs.a006124
Author(s):  
Beata Bessenyei ◽  
Istvan Balogh ◽  
Attila Mokanszki ◽  
Aniko Ujfalusi ◽  
Rolph Pfundt ◽  
...  

The MED13L-related intellectual disability or MRFACD syndrome (Mental retardation and distinctive facial features with or without cardiac defects; MIM # 616789) is one of the most common form of syndromic intellectual disability with about a hundred cases reported so far. Affected individuals share overlapping features comprising intellectual disability, hypotonia, motor delay, remarkable speech delay, and a recognizable facial gestalt. De novo disruption of the MED13L gene by deletions, duplications or sequence variants has been identified deleterious. Siblings affected by intragenic deletion transmitted from a mosaic parent have been reported once in the literature. We now present the first case of paternal germinal mosaicism for a missense MED13L variant causing MRFACD syndrome in one of the father's children and be the likely cause of intellectual disability and facial dysmorphism in the other. As part of the Mediator complex, the MED proteins have an essential role in regulating transcription. 32 subunits of the Mediator complex genes have been linked to congenital malformations that are now acknowledged as transcriptomopathies. The MRFACD syndrome has been suggested to represent a recognizable phenotype.


Blood ◽  
2012 ◽  
Vol 119 (23) ◽  
pp. 5575-5583 ◽  
Author(s):  
Norifumi Sawamukai ◽  
Atsushi Satake ◽  
Amanda M. Schmidt ◽  
Ian T. Lamborn ◽  
Priti Ojha ◽  
...  

Abstract FoxP3+ regulatory T cells (Tregs) suppress GVHD while preserving graft-versus-tumor effects, making them an attractive target for GVHD therapy. The donor-derived Treg pool can potentially be derived from the expansion of preexisting natural Tregs (nTregs) or from de novo generation of inducible Tregs (iTregs) from donor Tconvs in the transplantation recipient. Using an MHC-mismatched model of acute GVHD, in the present study we found that the Treg pool was comprised equally of donor-derived nTregs and iTregs. Experiments using various combinations of T cells from wild-type and FoxP3-deficient mice suggested that both preexisting donor nTregs and the generation of iTregs in the recipient mice contribute to protection against GVHD. Surprisingly, CD8+FoxP3+ T cells represented approximately 70% of the iTreg pool. These CD8+FoxP3+ T cells shared phenotypic markers with their CD4+ counterparts and displayed suppressive activity, suggesting that they were bona fide iTregs. Both CD4+ and CD8+ Tregs appeared to be protective against GVHD-induced lethality and required IL-2 and TGFβ receptor expression for their generation. These data illustrate the complex makeup of the donor-derived FoxP3+ Treg pool in allogeneic recipients and their potential role in protection against GVHD.


Author(s):  
Antoni Soriano-Arandes ◽  
Berta Ferran ◽  
Magda Campins ◽  
Juliana Esperalba-Esquerra ◽  
Juliana Reyes-Urueña ◽  
...  

We analyzed the characteristics of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infected children during lock-down period in Catalonia (Spain), and their transmission role within the households. Among 295 traced household contacts of 89 pediatric patients, children were classified as final index cases in only 3.4% of the traced homes.


2011 ◽  
Vol 33 (2) ◽  
pp. 355-358 ◽  
Author(s):  
Céline Bonnet ◽  
Alice Masurel-Paulet ◽  
Asma Ali Khan ◽  
Mylène Béri-Dexheimer ◽  
Patrick Callier ◽  
...  

2017 ◽  
Vol 07 (02) ◽  
pp. 074-077
Author(s):  
Pinar Arican ◽  
Dilek Cavusoglu ◽  
Pinar Gencpinar ◽  
Berk Ozyilmaz ◽  
Taha Ozdemir ◽  
...  

AbstractThe Xp11.22–p11.23 duplication syndrome was described in 2009 by Giorda et al and is characterized by intellectual disability, speech delay, and electroencephalography anomalies. We report a case of a 23-month-old girl who presented with epilepsy and global developmental delay and who had a small duplication at Xp11.23. The case we present here is the first case showing the clinical features of Xp11.22–p11.23 duplication syndrome only involving synovial sarcoma, X breakpoint (SSX) genes: SSX1, SSX3, SSX4, and SSX9. This case report contributes to an expanding clinical spectrum of Xp11.22–p11.23 duplication syndrome.


2014 ◽  
Vol 87 (4) ◽  
pp. 356-361 ◽  
Author(s):  
J. Nakajima ◽  
N. Okamoto ◽  
J. Tohyama ◽  
M. Kato ◽  
H. Arai ◽  
...  

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