scholarly journals Case Report: Congenital Brain Dysplasia, Developmental Delay and Intellectual Disability in a Patient With a 7q35-7q36.3 Deletion

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang-Liang Fan ◽  
Yue Sheng ◽  
Chen-Yu Wang ◽  
Ya-Li Li ◽  
Ji-Shi Liu
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
Developmental Delay ◽  
Candidate Genes ◽  
De Novo ◽  
Chromosome Region ◽  
Single Nucleotide Polymorphism Array ◽  
Chinese Patient ◽  
Terminal Deletion ◽  
Deletion Syndrome

7q terminal deletion syndrome is a rare condition presenting with multiple congenital malformations, including abnormal brain and facial structures, developmental delay, intellectual disability, abnormal limbs, and sacral anomalies. At least 40 OMIM genes located in the 7q34-7q36.3 region act as candidate genes for these phenotypes, of which SHH, EN2, KCNH2, RHEB, HLXB9, EZH2, MNX1 and LIMR1 may be the most important. In this study, we discuss the case of a 2.5-year-old male patient with multiple malformations, congenital brain dysplasia, developmental delay, and intellectual disability. A high-resolution genome-wide single nucleotide polymorphism array and real-time polymerase chain reaction were performed to detect genetic lesions. A de novo 9.4 Mb deletion in chromosome region 7q35-7q36.3 (chr7:147,493,985–156,774,460) was found. This chromosome region contains 68 genes, some of which are candidate genes for each phenotype. To the best of our knowledge, this is a rare case report of 7q terminal deletion syndrome in a Chinese patient. Our study identifies a rare phenotype in terms of brain structure abnormalities and cerebellar sulcus widening in patients with deletion in 7q35-7q36.3.

scholarly journals A novel de novo KDM5C variant in a female with global developmental delay and ataxia: a case report

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Natalie C. Lippa ◽  
Subit Barua ◽  
Vimla Aggarwal ◽  
Elaine Pereira ◽  
Jennifer M. Bain
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
Short Stature ◽  
Developmental Delay ◽  
De Novo ◽  
Phenotypic Variability ◽  
Missense Variant ◽  
Global Developmental Delay ◽  
Related Disorder ◽  
Patient Reported

Abstract Background Pathogenic variants in KDM5C are a cause of X-linked intellectual disability in males. Other features in males include short stature, dysmorphic features, seizures and spasticity. In some instances, female relatives were noted to have learning difficulties and mild intellectual disabilities, but full phenotypic descriptions were often incomplete. Recently, detailed phenotypic features of five affected females with de novo variants were described. (Clin Genet 98:43–55, 2020) Four individuals had a protein truncating variant and 1 individual had a missense variant. All five individuals had developmental delay/intellectual disability and three neurological features. Case presentation Here we report a three-year-old female with global developmental delay, hypotonia and ataxia. Through whole exome sequencing, a de novo c.1516A > G (p.Met506Val) variant in KDM5C was identified. This missense variant is in the jumonji-C domain of this multi domain protein where other missense variants have been previously reported in KDM5C related disorder. The KDM5C gene is highly intolerant to functional variation which suggests its pathogenicity. The probands motor delays and language impairment is consistent with other reported female patients with de novo variants in KDM5C. However, other features reported in females (distinctive facial features, skeletal abnormalities, short stature and endocrine features) were absent. To the best of our knowledge, our proband is the first female patient reported with a diagnosis of ataxia. Conclusions This case report provides evidence for an emerging and phenotypic variability that adds to the literature of the role of KDM5C in females with neurodevelopmental disorders as well as movement disorders.

Intragenic Deletion of the ZMYND11 Gene in 10p15.3 is Associated with Developmental Delay Phenotype: A Case Report

2021 ◽  
pp. 1-4
Author(s):  
Minh-Tuan Huynh ◽  
Cong Toai Tran ◽  
Madeleine Joubert ◽  
Claire Bénéteau
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
Developmental Delay ◽  
Clinical Features ◽  
Behavioral Problems ◽  
Gene Deletion ◽  
De Novo ◽  
Underlying Disease ◽  
Disease Mechanism ◽  
Intragenic Deletion

Submicroscopic 10p15.3 microdeletions were previously reported to be associated with developmental delay, and the smallest region of overlap of 10p15.3 deletion including <i>DIP2C</i> and <i>ZMYND11</i> was defined. Moreover, pathogenic <i>ZMYND11</i> truncating variants were subsequently identified in a cohort of patients with developmental delay. Of interest, patients harboring 10p15.3 microdeletions or pathogenic <i>ZMYND11</i> truncating variants share similar clinical features including hypotonia, intellectual disability, facial dysmorphisms, speech and motor delays, seizures, and significant behavioral problems. Only 1 patient with whole <i>ZMYND11</i> gene deletion was recorded, and no intragenic <i>ZMYND11</i> deletion was reported up to date. Here, we describe a 7-year-old boy with developmental delay, carrying the smallest de novo 10p15.3 microdeletion, harboring the 5′UTR and the first 2 exons of <i>ZMYND11.</i> Taken together, our report contributes to expand the clinical and mutational spectrum of <i>ZMYND11</i> and confirms haploinsufficiency as the underlying disease mechanism.

IL1RAPL1 Gene Deletion in a Female Patient with Developmental Delay and Continuous Spike-Wave during Sleep

2021 ◽  
Author(s):  
Evan Jiang ◽  
Mark P. Fitzgerald ◽  
Katherine L. Helbig ◽  
Ethan M. Goldberg
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Synapse Formation ◽  
De Novo ◽  
Interleukin 1 ◽  
Autism Spectrum ◽  
Neurological Dysfunction ◽  
Behavioral Disorder ◽  
Clinical Genetic ◽  
Severe Intellectual Disability

AbstractInterleukin-1 receptor accessory protein-like 1 (IL1RAPL1) encodes a protein that is highly expressed in neurons and has been shown to regulate neurite outgrowth as well as synapse formation and synaptic transmission. Clinically, mutations in or deletions of IL1RAPL1 have been associated with a spectrum of neurological dysfunction including autism spectrum disorder and nonsyndromic X-linked developmental delay/intellectual disability of varying severity. Nearly all reported cases are in males; in the few reported cases involving females, the clinical presentation was mild or the deletion was identified in phenotypically normal carriers in accordance with X-linked inheritance. Using genome-wide microarray analysis, we identified a novel de novo 373 kb interstitial deletion of the X chromosome (Xp21.1-p21.2) that includes exons 4 to 6 of the IL1RAPL1 gene in an 8-year-old girl with severe intellectual disability and behavioral disorder with a history of developmental regression. Overnight continuous video electroencephalography revealed electrical status epilepticus in sleep (ESES). This case expands the clinical genetic spectrum of IL1RAPL1-related neurodevelopmental disorders and highlights a new genetic association of ESES.

Genomic Syndromes in Schizophrenia

2013 ◽  
pp. 247-255
Author(s):  
George Kirov ◽  
Michael C. O’Donovan ◽  
Michael J. Owen
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variants ◽  
Individual Risk ◽  
Genomic Deletions ◽  
Pathogenic Cnvs ◽  
Cognition And Learning

Several submicroscopic genomic deletions and duplications known as copy number variants (CNVs) have been reported to increase susceptibility to schizophrenia. Those for which the evidence is particularly strong include deletions at chromosomal segments 1q21.1, 3q29, 15q11.2, 15q13.3, 17q12 and 22q11.2, duplications at 15q11.2-q13.1, 16p13.1, and 16p11.2, and deletions atthe gene NRXN1. The effect of each on individual risk is relatively large, but it does not appear that any of them is alone sufficient to cause disorder in carriers. These CNVs often arise as new mutations(de novo). Analyses of genes enriched among schizophrenia implicated CNVs highlight the involvement in the disorder of post-synaptic processes relevant to glutamatergicsignalling, cognition and learning. CNVs that contribute to schizophrenia risk also contribute to other neurodevelopmental disorders, including intellectual disability, developmental delay and autism. As a result of selection, all known pathogenic CNVs are rare, and none makes a sizeable contribution to overall population risk of schizophrenia, although the study of these mutations is nevertheless providing important insights into the origins of the disorder.

scholarly journals A De Novo Mutation in DYRK1A Causes Syndromic Intellectual Disability: A Chinese Case Report

2019 ◽  
Vol 10 ◽  
Author(s):  
Fengchang Qiao ◽  
Binbin Shao ◽  
Chen Wang ◽  
Yan Wang ◽  
Ran Zhou ◽  
...  
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
De Novo ◽  
De Novo Mutation ◽  
Chinese Case

Unusual Form of Obstructive Hydrocephalus in Association with 6q Terminal Deletion Syndrome: A Case Report and Literature Review

2019 ◽  
Vol 54 (6) ◽  
pp. 419-423 ◽  
Author(s):  
Hirofumi Iwamoto ◽  
Ai Muroi ◽  
Tomokazu Sekine ◽  
Takao Tsurubuchi ◽  
Eiichi Ishikawa ◽  
...  
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Obstructive Hydrocephalus ◽  
Terminal Deletion ◽  
Deletion Syndrome ◽  
Unusual Form

scholarly journals A Private 16q24.2q24.3 Microduplication in a Boy with Intellectual Disability, Speech Delay and Mild Dysmorphic Features

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 707 ◽  
Author(s):  
Orazio Palumbo ◽  
Pietro Palumbo ◽  
Ester Di Muro ◽  
Luigia Cinque ◽  
Antonio Petracca ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Chromosome Region ◽  
Snp Array ◽  
Supporting Evidence ◽  
Speech Delay ◽  
Dysmorphic Features ◽  
Phenotype Comparison ◽  
Molecular Comparison ◽  
Snp Array Analysis

No data on interstitial microduplications of the 16q24.2q24.3 chromosome region are available in the medical literature and remain extraordinarily rare in public databases. Here, we describe a boy with a de novo 16q24.2q24.3 microduplication at the Single Nucleotide Polymorphism (SNP)-array analysis spanning ~2.2 Mb and encompassing 38 genes. The patient showed mild-to-moderate intellectual disability, speech delay and mild dysmorphic features. In DECIPHER, we found six individuals carrying a “pure” overlapping microduplication. Although available data are very limited, genomic and phenotype comparison of our and previously annotated patients suggested a potential clinical relevance for 16q24.2q24.3 microduplication with a variable and not (yet) recognizable phenotype predominantly affecting cognition. Comparing the cytogenomic data of available individuals allowed us to delineate the smallest region of overlap involving 14 genes. Accordingly, we propose ANKRD11, CDH15, and CTU2 as candidate genes for explaining the related neurodevelopmental manifestations shared by these patients. To the best of our knowledge, this is the first time that a clinical and molecular comparison among patients with overlapping 16q24.2q24.3 microduplication has been done. This study broadens our knowledge of the phenotypic consequences of 16q24.2q24.3 microduplication, providing supporting evidence of an emerging syndrome.

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