Association of structural and numerical anomalies of chromosome 22 in a patient with syndromic intellectual disability

Naoufal, Rania; Legendre, Marine; Couet, Dominique; Gilbert‐Dussardier, Brigitte; Kitzis, Alain; Bilan, Frédéric; Harbuz, Radu

doi:10.1016/j.ejmg.2016.07.001

Cited by 4 publications

(5 citation statements)

References 25 publications

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“…The human chromosome 22q13 region is involved with various genetic and genomic disorders, including Phelan–McDermid syndrome (MIM 606232), in which terminal deletion of 22q13.3 encompassing the critical gene SHANK3 is frequently observed [1]. Occasionally, deletions proximal to the classical Phelan–McDermid syndrome region have been reported, affecting chromosome 22q13.2 without directly disrupting SHANK3 [2–4]. It remains unknown whether the abnormal neurodevelopmental phenotypes observed in patients with 22q13.2 deletions are caused by dysregulation of SHANK3 or haploinsufficiency of previously undefined “diseases genes” within the deletion.…”

Section: Introductionmentioning

confidence: 99%

De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith–Magenis syndrome

Vetrini¹,

McKee²,

Rosenfeld³

et al. 2019

Genome Med

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Background Neurodevelopmental disorders are genetically and phenotypically heterogeneous encompassing developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), structural brain abnormalities, and neurological manifestations with variants in a large number of genes (hundreds) associated. To date, a few de novo mutations potentially disrupting TCF20 function in patients with ID, ASD, and hypotonia have been reported. TCF20 encodes a transcriptional co-regulator structurally related to RAI1 , the dosage-sensitive gene responsible for Smith–Magenis syndrome (deletion/haploinsufficiency) and Potocki–Lupski syndrome (duplication/triplosensitivity). Methods Genome-wide analyses by exome sequencing (ES) and chromosomal microarray analysis (CMA) identified individuals with heterozygous, likely damaging, loss-of-function alleles in TCF20 . We implemented further molecular and clinical analyses to determine the inheritance of the pathogenic variant alleles and studied the spectrum of phenotypes. Results We report 25 unique inactivating single nucleotide variants/indels (1 missense, 1 canonical splice-site variant, 18 frameshift, and 5 nonsense) and 4 deletions of TCF20 . The pathogenic variants were detected in 32 patients and 4 affected parents from 31 unrelated families. Among cases with available parental samples, the variants were de novo in 20 instances and inherited from 4 symptomatic parents in 5, including in one set of monozygotic twins. Two pathogenic loss-of-function variants were recurrent in unrelated families. Patients presented with a phenotype characterized by developmental delay, intellectual disability, hypotonia, variable dysmorphic features, movement disorders, and sleep disturbances. Conclusions TCF20 pathogenic variants are associated with a novel syndrome manifesting clinical characteristics similar to those observed in Smith–Magenis syndrome. Together with previously described cases, the clinical entity of TCF20 -associated neurodevelopmental disorders (TAND) emerges from a genotype-driven perspective. Electronic supplementary material The online version of this article (10.1186/s13073-019-0623-0) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith–Magenis syndrome

Vetrini¹,

McKee²,

Rosenfeld³

et al. 2019

Genome Med

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“…Among them, only peer-reviewed studies in English were selected, divided in prenatal and postnatal and then sorted by year of publication. Postnatal studies reporting patients with complex rearrangements [ 12 , 13 , 14 ] or describing multiple cell lines [ 15 ] or providing insufficient evidence [ 16 ] were excluded from the postnatal cohort, along with papers that were not possible to retrieve. All cases described both prenatally and postnatally were counted once, leading to a final number of 28 articles being included, reporting a total of 18 prenatal and 25 postnatal cases.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, especially in postnatal settings, it is important to keep in mind that composite phenotypes might derive from the co-occurrence of complex rearrangements in association with mT22. Such reports have been previously described in the literature [ 13 , 14 , 46 , 74 ], and a detailed description of such cases goes beyond the scope of this review.…”

Section: Suggested Recommendations For the Management Of Suspected Mt...mentioning

confidence: 96%

Trisomy 22 Mosaicism from Prenatal to Postnatal Findings: A Case Series and Systematic Review of the Literature

Trevisan,

Meroni,

Leoni

et al. 2024

Genes

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Background: Among aneuploidies compatible with life, trisomy 22 mosaicism is extremely rare, and only about 25 postnatal and 18 prenatal cases have been described in the literature so far. The condition is mainly characterized by facial and body asymmetry, cardiac heart defects, facial dysmorphisms, growth failure, delayed puberty, and variable degrees of neurodevelopmental delay. Problem: The scattered information regarding the condition and the dearth of data on its natural history and developmental outcomes restrict genetic counseling, particularly in prenatal settings. Moreover, a prompt diagnosis is frequently delayed by the negative selection of trisomic cells in blood, with mosaicism percentage varying among tissues, which often entails the need for further testing. Purpose/topic: The aim of our work is to provide assistance in prenatal and postnatal genetic counseling by systematically delineating the current knowledge of the condition. This entails defining the prenatal and postnatal characteristics of the condition and presenting novel data from three cases, both prenatally and postnatally. Additionally, we report the developmental outcomes observed in two new patients.

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“…At the same time, the variety of authors note reduction in the severity of the left-sided asymmetry for one reason or another during the certain speech disorders (Key et al, 2007;Kurth et al, 2018;Naoufal et al, 2016;Wilson & Bishop, 2018). One of the most common causes associated with the growth of speech problems is called left-handedness (Nikolaeva et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

The Peculiarity of Lateral Preferences and the Quality of the Task Performance within the Go/Go Paradigm in Children with Complex Language Disabilities

Nikolaeva¹,

Брониславовна²,

Nikiforova³

2020

PSYCH

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The present study has tested the hypothesis of the connection of speech problems in children with left-handedness with the realisation of some high-speed reactions, in particular, a simple sensorimotor reaction in the paradigm of go/go. The handedness is determined on the basis of a set of tests; their results correlate with the results of dichotic testing. The study involves 90 children without any speech disorders and 47 children with complex speech disturbances (CSD). It is shown that the children with CSD are more likely to be not left-handed but mixed-handed in comparison with children with no speech disorders. The probability of speech diagnosis is connected with the mother's age at birth and her level of education. The older the mother at birth is and the higher the level of her education is, the less likelihood of speech diagnosis is. The children without any CSD are more steady and better at performing the task in the go/go paradigm in comparison with the children with CSD. The stability of the task performance is associated with the age of the parents. The older the father and mother are, the more effective the child without any CSD during the second part of the task works.

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Association of structural and numerical anomalies of chromosome 22 in a patient with syndromic intellectual disability

Cited by 4 publications

References 25 publications

De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith–Magenis syndrome

De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith–Magenis syndrome

Trisomy 22 Mosaicism from Prenatal to Postnatal Findings: A Case Series and Systematic Review of the Literature

The Peculiarity of Lateral Preferences and the Quality of the Task Performance within the Go/Go Paradigm in Children with Complex Language Disabilities

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