Rare Copy Number Variations and Predictors in Children With Intellectual Disability and Epilepsy

Смещение инактивации Х-хромосомы может быть следствием и маркером нарушения клеточной пролиферации при вариациях числа копий ДНК на Х-хромосоме. Х-сцепленные CNV выявляются как у женщин с невынашиванием беременности и смещением инактивации Х-хромосомы (с частотой 33,3%), так и у пациентов с умственной отсталостью и смещением инактивацией у их матерей (с частотой 40%). A skewed X-chromosome inactivation can be a consequence and a marker of impaired cell proliferation in the presence of copy number variations (CNV) on the X chromosome. X-linked CNVs are detected in women with miscarriages and a skewed X-chromosome inactivation (with a frequency of 33.3%), as well as in patients with intellectual disability and skewed X-chromosome inactivation in their mothers (with a frequency of 40%).

Download Full-text

A Case With 4 de Novo Copy Number Variations With Clinical Features That Overlap 1q43q44 Microdeletion and 3q29 Microduplication Syndromes

Child Neurology Open ◽

10.1177/2329048x18798200 ◽

2018 ◽

Vol 5 ◽

pp. 2329048X1879820

Author(s):

Miriam Kessi ◽

Jing Peng ◽

Lifen Yang ◽

Haolin Duan ◽

Yulin Tang ◽

...

Keyword(s):

Intellectual Disability ◽

Corpus Callosum ◽

Copy Number ◽

De Novo ◽

Copy Number Variations ◽

Language Delay ◽

Global Developmental Delay ◽

Recurrent Infections ◽

Dental Anomalies ◽

Microdeletion Syndrome

1q43q44 microdeletion syndrome is characterized by intellectual disability/global developmental delay, epilepsy, dysmorphic facies, stereotypic movement, language delay, recurrent infections, dental anomalies, and hand and foot anomalies. Microcephaly and corpus callosum dysplasia are present in some cases depending on gene content. 3q29 microduplication syndrome is characterized by intellectual disability, language delay, microcephaly, and dental anomalies. We report the first case with 4 de novo copy number variations with clinical features which overlap 1q43q44 microdeletion and 3q29 microduplication syndromes. Our case presented with global developmental delay, epilepsy, recurrent infections, stereotypic movements, speech delay, microcephaly, facial dysmorphism, bilateral clinodactyly, and small puffy feet with metatarsus varus; however, she had no corpus callosum dysplasia. Our case highlights the role of multiple copy number variations in the occurrence of a certain phenotype. Moreover, it supports the theory that the loss of HNRNPU gene function cannot explain the occurrence of microcephaly and abnormalities of the corpus callosum in 1q43q44 microdeletion syndrome.

Download Full-text

A Multicentric Brazilian Investigative Study of Copy Number Variations in Patients with Congenital Anomalies and Intellectual Disability

Scientific Reports ◽

10.1038/s41598-018-31754-2 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

J. R. M. Ceroni ◽

R. L. Dutra ◽

R. S. Honjo ◽

J. C. Llerena ◽

A. X. Acosta ◽

...

Keyword(s):

Intellectual Disability ◽

Congenital Anomalies ◽

Copy Number ◽

Copy Number Variations

Download Full-text

Interstitial deletion of 3p22.3p22.2 encompassingARPP21andCLASP2is a potential pathogenic factor for a syndromic form of intellectual disability: A co-morbidity model with additional copy number variations in a large family

American Journal of Medical Genetics Part A ◽

10.1002/ajmg.a.36257 ◽

2013 ◽

Vol 161 (11) ◽

pp. 2890-2893 ◽

Cited By ~ 5

Author(s):

Giuseppe Marangi ◽

Daniela Orteschi ◽

Valentina Milano ◽

Giorgia Mancano ◽

Marcella Zollino

Keyword(s):

Intellectual Disability ◽

Copy Number ◽

Large Family ◽

Copy Number Variations ◽

Interstitial Deletion ◽

Pathogenic Factor ◽

Co Morbidity

Download Full-text

Phenotypic and Molecular Cytogenetic Analysis of a Case of Monosomy 1p36 Syndrome due to Unbalanced Translocation

Molecular Syndromology ◽

10.1159/000510428 ◽

2020 ◽

Vol 11 (5-6) ◽

pp. 284-295

Author(s):

Dalia F. Hussen ◽

Alaa K. Kamel ◽

Mona K. Mekkawy ◽

Engy A. Ashaat ◽

Mona O. El Ruby

Keyword(s):

Intellectual Disability ◽

Microarray Analysis ◽

Cytogenetic Analysis ◽

Copy Number ◽

Clinical Manifestations ◽

Copy Number Variations ◽

Chromosomal Microarray Analysis ◽

Fish Analysis ◽

Unbalanced Translocation ◽

Genotype Correlation

Monosomy 1p36 syndrome is one of the most common submicroscopic deletion syndromes, which is characterized by the presence of delayed developmental milestones, intellectual disability, and clinically recognizable dysmorphic craniofacial features. The syndrome comprises 4 cytogenetic groups including pure terminal deletions, interstitial deletions, complex rearrangements, and derivative chromosomes 1 due to unbalanced translocations, where unbalanced translocations represent the least percentage of all cases of monosomy 1p36 (7%). Most patients with monosomy 1p36 due to an unbalanced translocation can be cytogenetically diagnosed using conventional techniques. However, chromosomal microarray analysis is mandatory in these cases to detect copy number variance and size of the deletion and allows for setting a phenotype-genotype correlation. Here, we studied a 1.5-year-old female patient who showed intellectual disability, delayed milestones, hypotonia, seizures, and characteristic dysmorphic features including brachycephaly, straight eyebrows, deep-set eyes, downslanting palpebral fissures, midface hypoplasia, depressed nasal bridge, long philtrum, and pointed chin. Conventional cytogenetic analysis (CCA), microarray study, and fluorescence in situ hybridization (FISH) analysis were performed. CCA showed a translocation involving chromosomes 1 and 21, 45,XX,der(1)t(1;21)(p36.32;q21.1)dn. Microarray analysis revealed copy number losses at both 1p36 and proximal 21q. FISH confirmed the presence of the 1p36 deletion, but was not performed for 21q. We have concluded that phenotype-genotype correlation for monosomy 1p36 syndrome can be performed for the fundamental clinical manifestations; however, the final aspect of the syndrome depends on composite factors. Monosomy 1p36 due to unbalanced translocation may present either classically or with additional altered features of various severity based on the copy number variations involving different chromosomes.

Download Full-text

miRNA and miRNA target genes in copy number variations occurring in individuals with intellectual disability

BMC Genomics ◽

10.1186/1471-2164-14-544 ◽

2013 ◽

Vol 14 (1) ◽

pp. 544 ◽

Cited By ~ 12

Author(s):

Ying Qiao ◽

Chansonette Badduke ◽

Eloi Mercier ◽

Suzanne ME Lewis ◽

Paul Pavlidis ◽

...

Keyword(s):

Intellectual Disability ◽

Copy Number ◽

Mirna Target ◽

Target Genes ◽

Copy Number Variations

Download Full-text

Xp11.2 Duplication in Females: Unique Features of a Rare Copy Number Variation

Frontiers in Genetics ◽

10.3389/fgene.2021.635458 ◽

2021 ◽

Vol 12 ◽

Author(s):

Márta Czakó ◽

Ágnes Till ◽

Judith Zima ◽

Anna Zsigmond ◽

András Szabó ◽

...

Keyword(s):

Intellectual Disability ◽

Copy Number Variation ◽

Copy Number ◽

Neurodevelopmental Disorder ◽

Copy Number Variations ◽

Pathogenic Role ◽

Routine Application ◽

Phenotype Analysis ◽

Number Variation ◽

Minor Anomalies

Among the diseases with X-linked inheritance and intellectual disability, duplication of the Xp11.23p11.22 region is indeed a rare phenomenon, with less than 90 cases known in the literature. Most of them have been recognized with the routine application of array techniques, as these copy number variations (CNVs) are highly variable in size, occurring in recurrent and non-recurrent forms. Its pathogenic role is not debated anymore, but the information available about the pathomechanism, especially in affected females, is still very limited. It has been observed that the phenotype in females varies from normal to severe, which does not correlate with the size of the duplication or the genes involved, and which makes it very difficult to give an individual prognosis. Among the patients studied by the authors because of intellectual disability, epilepsy, and minor anomalies, overlapping duplications affecting the Xp11.23p11.22 region were detected in three females. Based on our detailed phenotype analysis, we concluded that Xp11.23p11.22 duplication is a neurodevelopmental disorder.

Download Full-text

Comprehensive genome sequencing analyses identify novel gene mutations and copy number variations associated with infant developmental delay or intellectual disability (DD/ID)

Genes & Diseases ◽

10.1016/j.gendis.2021.11.008 ◽

2021 ◽

Author(s):

Yuxia Chen ◽

Xiang Tang ◽

Ling Liu ◽

Qinrong Huang ◽

Li Lin ◽

...

Keyword(s):

Intellectual Disability ◽

Developmental Delay ◽

Genome Sequencing ◽

Copy Number ◽

Gene Mutations ◽

Copy Number Variations ◽

Novel Gene

Download Full-text

Novel deletion of exon 3 in TYR gene causing Oculocutaneous albinism 1B in an Indian family along with intellectual disability associated with chromosomal copy number variations

BMC Medical Genomics ◽

10.1186/s12920-021-01152-1 ◽

2022 ◽

Vol 15 (1) ◽

Author(s):

Somprakash Dhangar ◽

Purvi Panchal ◽

Jagdeeshwar Ghatanatti ◽

Jitendra Suralkar ◽

Anjali Shah ◽

...

Keyword(s):

Intellectual Disability ◽

Copy Number ◽

Clinical Presentation ◽

Array Cgh ◽

Copy Number Variations ◽

Oculocutaneous Albinism ◽

Male Child ◽

Heterozygous Deletion ◽

Indian Family ◽

Chromosomal Copy Number

Abstract Background Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by hypo-pigmentation of skin, hair, and eyes. The OCA clinical presentation is due to a deficiency of melanin biosynthesis. Intellectual disability (ID) in OCA cases is a rare clinical presentation and appropriate diagnosis of ID is challenging through clinical examination. We report an Indian family with a rare co-inheritance of OCA1B and ID due to a novel TYR gene variant and chromosomal copy number variations. Methods We have done a study on three siblings (2 males and 1 female) of a family where all of them presented with hypopigmented skin, hair and eyes. The male children and their father was affected with ID. Targeted exome sequencing and multiplex ligation-dependent probe amplification analysis were carried out to identify the OCA1B and ID associated genomic changes. Further Array-CGH was performed using SurePrint G3 Human CGH + SNP, 8*60 K array. Results A rare homozygous deletion of exon 3 in TYR gene causing OCA1B was identified in all three children. The parents were found to be heterozygous carriers. The Array-CGH analysis revealed paternally inherited heterozygous deletion(1.9 MB) of 15q11.1-> 15q11.2 region in all three children. Additionally, paternally inherited heterozygous deletion(2.6 MB)of 10q23.2-> 10q23.31 region was identified in the first male child; this may be associated with ID as the father and the child both presented with ID. While the 2nd male child had a denovo duplication of 13q31.1-> 13q31.3 chromosomal region. Conclusion A rare homozygous TYR gene exon 3 deletion in the present study is the cause of OCA1B in all three children, and the additional copy number variations are associated with the ID. The study highlights the importance of combinational genetic approaches for diagnosing two different co-inherited disorders (OCA and ID). Hence, OCA cases with additional clinical presentation need to be studied in-depth forthe appropriate management of the disease.

Download Full-text