scholarly journals First Report of a de novo 10q23.31q23.33 Microdeletion: Obesity, Intellectual Disability and Microcephaly

2021 ◽  
pp. 1-5
Author(s):  
Ayberk Turkyilmaz ◽  
Erdal Kurnaz ◽  
Atilla Cayir
Keyword(s):  
Intellectual Disability ◽  
Array Cgh ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Autism Spectrum ◽  
Comparative Genomic ◽  
Facial Dysmorphism ◽  
Genetic And Environmental Factors

Intellectual disability (ID) is characterized by limited or insufficient development of mental abilities, including intellectual functioning impairments, such as learning and understanding cause-effect relationships. Some cases have ID as the only finding and are called isolated cases. Conversely, cases accompanied by facial dysmorphism, microcephaly, autism spectrum disorder, epilepsy, obesity, and congenital anomalies are called syndromic developmental delay (DD)/ID. Isolated and syndromic DD/ID cases show extreme genetic heterogeneity. Genetic etiology can be detected in approximately 40% of the cases, whereas chromosomal abnormalities are observed in 25%. Obesity is a multifactorial disease in which both genetic and environmental factors play important roles. The role of heredity in obesity has been reported to be between 40 and 70%. Array-based comparative genomic hybridization (array-CGH) can detect CNVs in the whole genome at a higher resolution than conventional cytogenetic methods. Array-CGH is currently recommended as the first-tier genetic test for ID cases worldwide. In the present study, we aimed to evaluate clinical, radiological, and genetic analyses of a 12-year and 4-month-old girl with microcephaly, ID, and obesity. In the array-CGH analysis, a 3.1-Mb deletion, arr[GRGh37] 10q23.31g23.33 (92745793_95937944)×1 was detected, and this alteration was evaluated to be pathogenic. We consider that haploinsufficiency of the candidate genes (<i>GPR120</i>, <i>KIF11</i>, <i>EXOC6</i>, <i>CYP26A1</i>, <i>CYP26C1</i>, and <i>LGI1</i>) in the deletion region may explain microcephaly, ID, obesity, seizures, and ophthalmological findings in our patient. The investigation of 10q23.31q23.33 microdeletion in cases with syndromic obesity may contribute to molecular genetic diagnosis.

scholarly journals Genetic Diagnosis of Chromosomal Congenital Anomalies in Albanian Pediatric Patients by Array CGH

2017 ◽  
Vol 5 (5) ◽  
pp. 587-591
Author(s):  
Anila Babameto-Laku ◽  
Dorina Roko ◽  
Gentian Vyshka
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Congenital Anomalies ◽  
Array Cgh ◽  
International System ◽  
Genetic Diagnosis ◽  
Case Series ◽  
Comparative Genomic ◽  
Facial Dysmorphism ◽  
Chromosomal Anomalies

AIM: The aim of our study was to identify chromosomal imbalances by whole-genome microarray-based comparative genomic hybridization (array CGH) in DNA samples of children in which karyotype results cannot be obtained. The present paper describes the first Albanian experience of an array CGH application.MATERIAL AND METHODS: The cohort included seven children with developmental delay or intellectual disability, facial dysmorphism and congenital anomalies according to clinical criteria, suggestive of chromosomal anomalies. The age range was from newborn to five years old. The cytogenetic analysis determined by a standard method of G-banding according to the International System for Human Cytogenetic Nomenclature (ISCN 2005) was performed for all our patients, while array CGH was performed on genomic DNA isolated from the blood of 7 cases.RESULTS: Among the seven patients analysed with array CGH, three patients resulted in duplication and one deletion, one patient with a microdeletion and three patients with duplication. Array CGH facilitated the recognition of submicroscopic deletions and duplications as risk factors for genetic diagnosis in all our patients.CONCLUSIONS: Our case series with congenital chromosomal anomalies confirms the high diagnostic value of the method, as suggested by previous studies. The technique must be available also in less developed countries, to significantly improve the genetic diagnosis of paediatric patients with developmental delay or intellectual disability, congenital anomalies and dysmorphic features. The identification of chromosomal abnormalities in these patients and the genetic counselling will provide family members with an explanation for their child’s developmental disability or birth defect, allowing better information about recurrence risks, and permit the anticipation of certain medical problems that require intervention.

scholarly journals An Indian infant with de novo duplication of 16p chromosome: A rare genetic syndrome

2020 ◽  
Vol 0 ◽  
pp. 1-3
Author(s):  
Manisha Goyal ◽  
Ashok Gupta ◽  
Mohammed Faruq ◽  
Divya Shrivastava
Keyword(s):  
Array Cgh ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Comparative Genomic ◽  
Facial Dysmorphism ◽  
Genetic Syndromes ◽  
Genetic Syndrome ◽  
Diagnostic Technology ◽  
Chromosome 16P13.3 ◽  
Indian Infant

Facial dysmorphism along with multiple congenital anomalies is observed in many genetic syndromes mostly in chromosomal microdeletion or duplication, which cannot be detected by conventional karyotype. Here, we report a case with facial dysmorphism, cleft palate, congenital heart defect, and umbilical hernia, diagnosed with duplication at chromosome 16p13.3 by array comparative genomic hybridization (CGH) at very early age. Array CGH is the advanced diagnostic technology; enable to diagnose chromosomal abnormalities earlier thus can provide appropriate medical management and prognostication.

scholarly journals Identification of Copy Number Variation by Array-CGH in Portuguese Children and Adolescents Diagnosed with Autism Spectrum Disorders

2019 ◽  
Vol 50 (06) ◽  
pp. 367-377
Author(s):  
S. Monteiro ◽  
J. Pinto ◽  
A. Mira Coelho ◽  
M. Leão ◽  
S. Dória
Keyword(s):  
Autism Spectrum Disorders ◽  
Copy Number ◽  
Array Cgh ◽  
Chromosomal Abnormalities ◽  
Daily Practice ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Uncertain Significance ◽  
Spectrum Disorders

Background Autism spectrum disorders (ASD) affect many children with an estimated prevalence of 1%. Array-comparative genomic hybridization (CGH) offers significant sensitivity for the identification of submicroscopic chromosomal abnormalities and it is one of the most used techniques in daily practice. The main objective of this study was to describe the usefulness of array-CGH in the etiologic diagnosis of ASD. Methods Two-hundred fifty-three patients admitted to a neurogenetic outpatient clinic and diagnosed with ASD were selected for array-CGH (4 × 180K microarrays). Public databases were used for classification in accordance with the American College of Medical Genetics Standards and Guidelines. Results About 3.56% (9/253) of copy number variations (CNVs) were classified as pathogenic. When likely pathogenic CNVs were considered, the rate increased to 11.46% (29/253). Some CNVs apparently not correlated to the ASD were also found. Considering a phenotype–genotype correlation, the patients were divided in two groups. One group according to previous literature includes all the CNVs related to ASDs (23 CNVs present in 22 children) and another with those apparently not related to ASD (10 CNVs present in 7 children). In 18 patients, a next-generation sequencing (NGS) panel were performed. From these, one pathogenic and 16 uncertain significance variants were identified. Conclusion The results of our study are in accordance with the literature, highlighting the relevance of array-CGH in the genetic of diagnosis of ASD population, namely when associated with other features. Our study also reinforces the need for complementarity between array-CGH and NGS panels or whole exome sequencing in the etiological diagnosis of ASD.

scholarly journals A 9-year-old-girl with Phelan McDermid Syndrome, who had been diagnosed with an autism spectrum disorder

2016 ◽  
Vol 19 (2) ◽  
pp. 85-90 ◽  
Author(s):  
I Görker ◽  
H Gürkan ◽  
S Demir Ulusal ◽  
E Atlı ◽  
E Ikbal Atlı
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Comparative Genomic ◽  
Parental Origin ◽  
Mild Intellectual Disability ◽  
First Case

AbstractPhelan McDermid Syndrome (PHMDS) (OMIM #606232), is a contiguous gene disorder resulting from deletion of the distal long arm of chromosome 22. The 22q13.3 deletions and mutations that lead to a loss of a functional copy of SHANK3 (OMIM *606230) cause the syndrome, characterized by moderate to profound intellectual disability, severely delayed or absent speech, hypotonia, and autism spectrum disorder (ASD) or ASD traits. In this study, we present the case of a 9-year-old girl who had earlier been diagnosed with an ASD. Our findings were a clinically mild intellectual disability, rounded face, pointed chin but no autistic findings. We learned that her neuromotor development was delayed and she had neonatal hypotonia in her history. A heterozygous deletion of MLC1, SBF1, MAPK8IP2, ARSA, SHANK3 and ACR genes, located on 22q13.33, was defined by multiplex ligation-dependent probe amplification (MLPA). Deletion of 22q13.3 (ARSA) region was confirmed by a fluorescent in situ hybridization (FISH) technique. The 22q13.3 deletion was found to be de novo in our patient, and she was diagnosed with PHMDS. We confirmed the 22q13.3 deletion and also determined a gain of 8p23.3-23.2 by array comparative genomic hybridization (aCGH). Fluorescent in situ hybridization was performed to determine whether the deletion was of parental origin and to identify regions of chromosomes where the extra 8p may have been located. The parents were found to be normal. The extra copy of 8p was observed on 22q in the patient. She is the first case reported in association with the 22q deletion of 8p duplications in the literature.

scholarly journals A novel de novo hemizygous ARHGEF9 mutation associated with severe intellectual disability and epilepsy: a case report

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110583
Author(s):  
Tong Qiu ◽  
Qian Dai ◽  
Qiu Wang
Keyword(s):  
Intellectual Disability ◽  
Exome Sequencing ◽  
Developmental Delay ◽  
De Novo ◽  
Clinical Symptoms ◽  
Genetic Diagnosis ◽  
Epileptic Seizures ◽  
Autism Spectrum ◽  
Loss Of Function ◽  
Severe Intellectual Disability

ARHGEF9 encodes collybistin, a brain-specific guanosine diphosphate-guanosine-5′-triphosphate exchange factor that plays an important role in clustering of gephyrin and γ-aminobutyric acid type A receptors in the postsynaptic membrane. Overwhelming evidence suggests that defects in this protein can cause X-linked intellectual disability, which comprises a series of clinical phenotypes, including autism spectrum disorder, behavior disorder, intellectual disability, and febrile seizures. Here, we report a boy with clinical symptoms of severe intellectual disability, epilepsy, and developmental delay and regression. Trio exome sequencing ( trio-clinical exome sequencing) identified a novel hemizygous deletion, c.656_c.669delACTTCTTTGAGGCC (p. His219Leu fs*9), in exon 5 of ARHGEF9. This variant was not reported in either the Genome Aggregation Database or our database of 309 patients with neurodevelopmental disorders. Oxcarbazepine and levetiracetam reduced the frequency of the patient’s epileptic seizures to a certain extent, but psychomotor developmental delay and developmental regression became more obvious with age. This case study seeks to report a de novo loss-of-function mutation of ARHGEF9, aiming to emphasize the genetic diagnosis of X-linked intellectual disability and further improve knowledge of the ethnic distribution of ARHGEF9 mutations.

6q13q14.3 Microdeletion Syndrome with Severe Hypotonia and Facial Dysmorphism: Genotype–Phenotype Correlation

2021 ◽  
Author(s):  
Manisha Goyal ◽  
Mohammed Faruq ◽  
Ashok Gupta ◽  
Divya Shrivastava ◽  
Uzma Shamim
Keyword(s):  
Array Cgh ◽  
Chromosomal Abnormalities ◽  
Comparative Genomic ◽  
Facial Dysmorphism ◽  
Genetic Syndromes ◽  
Phenotype Correlation ◽  
Microdeletion Syndrome ◽  
Genetic Syndrome ◽  
Severe Hypotonia ◽  
Diagnostic Technologies

AbstractHypotonia is a symptom of diminished tone of skeletal muscle and can be nongenetic or a part of genetic syndrome. Hypotonia, developmental delay, and facial dysmorphism are nonspecific findings observed in many genetic syndromes mostly in chromosomal microdeletion and duplication. Here we report a case with severe hypotonia and facial dysmorphism, diagnosed with deletion at 6q13q14.3 by array comparative genomic hybridization (CGH) at very early age. Recent genetic diagnostic technologies such as array CGH may enable clinicians to diagnose chromosomal abnormalities earlier and provide appropriate medical management

scholarly journals Identification of de novo mutations for ARID1B haploinsufficiency associated with Coffin–Siris syndrome 1 in three Chinese families via array-CGH and whole exome sequencing

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Guanting Lu ◽  
Qiongling Peng ◽  
Lianying Wu ◽  
Jian Zhang ◽  
Liya Ma
Keyword(s):  
Intellectual Disability ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Array Cgh ◽  
De Novo ◽  
Current Knowledge ◽  
Comparative Genomic ◽  
De Novo Mutations ◽  
Single Nucleotide Variants ◽  
Whole Exome

Abstract Background Coffin–Siris syndrome (CSS) is a multiple malformation syndrome characterized by intellectual disability associated with coarse facial features, hirsutism, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. CSS represents a small group of intellectual disability, and could be caused by at least twelve genes. The genetic background is quite heterogenous, making it difficult for clinicians and genetic consultors to pinpoint the exact disease types. Methods Array-Comparative Genomic Hybridization (array-CGH) and whole exome sequencing (WES) were applied for three trios affected with intellectual disability and clinical features similar with those of Coffin–Siris syndrome. Sanger sequencing was used to verify the detected single-nucleotide variants (SNVs). Results All of the three cases were female with normal karyotypes of 46, XX, born of healthy, non-consanguineous parents. A 6q25 microdeletion (arr[hg19]6q25.3(155,966,487–158,803,979) × 1) (2.84 Mb) (case 1) and two loss-of-function (LoF) mutations of ARID1B [c.2332 + 1G > A in case 2 and c.4741C > T (p.Q1581X) in case 3] were identified. All of the three pathogenic abnormalities were de novo, not inherited from their parents. After comparison of publicly available microdeletions containing ARID1B, four types of microdeletions leading to insufficient production of ARID1B were identified, namely deletions covering the whole region of ARID1B, deletions covering the promoter region, deletions covering the termination region or deletions covering enhancer regions. Conclusion Here we identified de novo ARID1B mutations in three Chinese trios. Four types of microdeletions covering ARID1B were identified. This study broadens current knowledge of ARID1B mutations for clinicians and genetic consultors.

scholarly journals A Rare, Recurrent,De Novo14q32.2q32.31 Microdeletion of 1.1 Mb in a 20-Year-Old Female Patient with a Maternal UPD(14)-Like Phenotype and Intellectual Disability

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Almira Zada ◽  
Farmaditya E. P. Mundhofir ◽  
Rolph Pfundt ◽  
Nico Leijsten ◽  
Willy Nillesen ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Female Patient ◽  
De Novo ◽  
Fragile X ◽  
Genetic Diagnosis ◽  
Facial Dysmorphism ◽  
Feeding Problems ◽  
Motor Delay ◽  
Genome Wide ◽  
Low Copy Repeats

We present a 20-year-old female patient from Indonesia with intellectual disability (ID), proportionate short stature, motor delay, feeding problems, microcephaly, facial dysmorphism, and precocious puberty who was previously screened normal for conventional karyotyping, fragile X testing, and subtelomeric MLPA analysis. Subsequent genome wide array analysis was performed on DNA from blood and revealed a 1.1 Mb deletion in 14q32.2q32.31 (chr14:100,388,343-101,506,214; hg19). Subsequent carrier testing in the parents by array showed that the deletion had occurredde novoin the patient and that her paternal 14q32 allele was deleted. The deleted region encompasses theDLK1/GTL2imprinted gene cluster which is consistent with the maternal UPD(14)-like phenotype of the patient. This rare, recurrent microdeletion was recently shown not to be mediated by low copy repeats, but by expanded TGG repeats, flanking the 14q32.2q32.21 deletion boundaries, a novel mechanism of recurrent genomic rearrangement. This is another example how the application of high resolution genome wide testing provides an accurate genetic diagnosis, thereby improving the care for patients and optimizing the counselling for family.

Epileptic Seizures Associated with Chromosomal Abnormalities Detected by Array Comparative Genomic Hybridization in Five Albanian Children

2017 ◽  
Vol 06 (03) ◽  
pp. 156-160
Author(s):  
Anila Babameto-Laku ◽  
Serla Grabova ◽  
Jera Kruja ◽  
Gentian Vyshka
Keyword(s):  
Intellectual Disability ◽  
Comparative Genomic Hybridization ◽  
Diagnostic Tool ◽  
Array Cgh ◽  
Chromosomal Abnormalities ◽  
Case Reports ◽  
Epileptic Seizures ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Novel Technologies

AbstractEpilepsy is an ever-changing field of research, with genetics and genomics playing a very important role in recent times. Novel technologies detecting chromosomal aberrations are applied widely, and array-based comparative genomic hybridization (array CGH) has become a basic diagnostic tool in a variety of neurologic and neuropsychiatric conditions. The authors describe five Albanian children suffering from epilepsy and screened for genetic problems using array CGH and other methods. A thorough neurological examination and imaging studies were performed for all patients, who in addition to seizures, suffered from diverse medical conditions such as microcephaly, developmental delay, intellectual disability, dysmorphic features, heart anomalies, cryptorchidism, and other clinical stigmata of an aberrant neurodevelopment. It is evident from our case reports that the array CGH as a diagnostic tool in molecular genetics has facilitated the recognition of microdeletions and microduplications as risk factors for both generalized and focal epilepsies. This method, therefore, clearly has a practical and scientific value in the investigation of children with epilepsy and associated intellectual disability and congenital anomalies.

scholarly journals Screening of 50 Cypriot Patients with Autism Spectrum Disorders or Autistic Features Using 400K Custom Array-CGH

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Ludmila Kousoulidou ◽  
Maria Moutafi ◽  
Paola Nicolaides ◽  
Stavros Hadjiloizou ◽  
Christos Christofi ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Developmental Disorders ◽  
Array Cgh ◽  
De Novo ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Normal Individuals ◽  
Spectrum Disorders ◽  
Clinical Description

Autism spectrum disorders (ASDs) comprise a distinct entity of neurodevelopmental disorders with a strong genetic component. Despite the identification of several candidate genes and causative genomic copy number variations (CNVs), the majority of ASD cases still remain unresolved. We have applied microarray-based comparative genomic hybridization (array-CGH) using Agilent 400K custom array in the first Cyprus population screening for identification of ASD-associated CNVs. A cohort of 50 ASD patients (G1), their parents (G2), 50 ethnically matched normal controls (G3), and 80 normal individuals having children with various developmental and neurological conditions (G4) were tested. As a result, 14 patients were found to carry 20 potentially causative aberrations, two of which werede novo. Comparison of the four population groups revealed an increased rate of rare disease-associated variants in normal parents of children with autism. The above data provided additional evidence, supporting the complexity of ASD aetiology in comparison to other developmental disorders involving cognitive impairment. Furthermore, we have demonstrated the rationale of a more targeted approach combining accurate clinical description with high-resolution population-oriented genomic screening for defining the role of CNVs in autism and identifying meaningful associations on the molecular level.

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