scholarly journals Clinical Report of a 17q12 Microdeletion with Additionally Unreported Clinical Features

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Jennifer L. Roberts ◽  
Stephanie K. Gandomi ◽  
Melissa Parra ◽  
Ira Lu ◽  
Chia-Ling Gau ◽  
...  
Keyword(s):  
De Novo ◽  
Abdominal Ultrasound ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Clinical Report ◽  
Snp Analysis ◽  
New Genotype ◽  
Compulsive Behaviors ◽  
Oppositional Defiance

Copy number variations involving the 17q12 region have been associated with developmental and speech delay, autism, aggression, self-injury, biting and hitting, oppositional defiance, inappropriate language, and auditory hallucinations. We present a tall-appearing 17-year-old boy with marfanoid habitus, hypermobile joints, mild scoliosis, pectus deformity, widely spaced nipples, pes cavus, autism spectrum disorder, intellectual disability, and psychiatric manifestations including physical and verbal aggression, obsessive-compulsive behaviors, and oppositional defiance. An echocardiogram showed borderline increased aortic root size. An abdominal ultrasound revealed a small pancreas, mild splenomegaly with a 1.3 cm accessory splenule, and normal kidneys and liver. A testing panel for Marfan, aneurysm, and related disorders was negative. Subsequently, a 400 K array-based comparative genomic hybridization (aCGH) + SNP analysis was performed which identified ade novosuspected pathogenic deletion on chromosome 17q12 encompassing 28 genes. Despite the limited number of cases described in the literature with 17q12 rearrangements, our proband’s phenotypic features both overlap and expand on previously reported cases. Since syndrome-specific DNA sequencing studies failed to provide an explanation for this patient’s unusual habitus, we postulate that this case represents an expansion of the 17q12 microdeletion phenotype. Further analysis of the deleted interval is recommended for new genotype-phenotype correlations.

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.

Autism spectrum mixed neurodevelopmental disorder associated with 6q27 deletion and multiple copies within 20q11.23: a case study

2014 ◽  
Vol 8 (3) ◽  
pp. 210-215
Author(s):  
Stephen Hopkins ◽  
Jeremy Turk ◽  
Adeniyi Daramola ◽  
Marinos Kyriakopoulos
Keyword(s):  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Content Type ◽  
Effective Strategies ◽  
Wide Range ◽  
Multiple Copies

Purpose – Copy Number Variations (CNVs) are not infrequently observed in aberrant neurodevelopment. CNVs can alter gene expression and have been linked to a wide range of neuropsychiatric disorders. The purpose of this case study is to report the association of CNVs with a mixed neurodevelopmental disorder. Design/methodology/approach – Array-Comparative Genomic Hybridisation analysis was carried out in a case of an eight-year-old boy presenting with a mixed neurodevelopmental disorder including autism spectrum disorder, intellectual disability, tic disorder, anxiety and severe aggression. The child's parents also underwent the same investigation. Findings – A 6q27 deletion and multiple copies within 20q11.23 were identified. The boy's father shared the 6q27 deletion and his mother also had multiple copies within 20q11.23. Originality/value – This is the first report linking the combination of 6p27 and 20q11 CNVs with a mixed neurodevelopmental presentation. Identifying CNVs that may underlie aberrant neurodevelopment is likely to assist in unravelling the aetiology of neurodevelopmental and psychiatric disorders and lead to more effective strategies for their characterisation and management.

scholarly journals Associations between Familial Rates of Psychiatric Disorders and De Novo Genetic Mutations in Autism

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Kyleen Luhrs ◽  
Tracey Ward ◽  
Caitlin M. Hudac ◽  
Jennifer Gerdts ◽  
Holly A. F. Stessman ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Copy Number ◽  
Depressive Disorders ◽  
De Novo ◽  
Familial Risk ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Genetic Etiology ◽  
Additive Contribution ◽  
Familial Risk Factors

The purpose of this study was to examine the confluence of genetic and familial risk factors in children with Autism Spectrum Disorder (ASD) with distinct de novo genetic events. We hypothesized that gene-disrupting mutations would be associated with reduced rates of familial psychiatric disorders relative to structural mutations. Participants included families of children with ASD in four groups: de novo duplication copy number variations (DUP, n=62), de novo deletion copy number variations (DEL, n=74), de novo likely gene-disrupting mutations (LGDM, n=267), and children without a known genetic etiology (NON, n=2111). Familial rates of psychiatric disorders were calculated from semistructured interviews. Results indicated overall increased rates of psychiatric disorders in DUP families compared to DEL and LGDM families, specific to paternal psychiatric histories, and particularly evident for depressive disorders. Higher rates of depressive disorders in maternal psychiatric histories were observed overall compared to paternal histories and higher rates of anxiety disorders were observed in paternal histories for LGDM families compared to DUP families. These findings support the notion of an additive contribution of genetic etiology and familial factors are associated with ASD risk and highlight critical need for continued work targeting these relationships.

scholarly journals Increased Frequency of Copy Number Variations Revealed by Array Comparative Genomic Hybridization in the Offspring of Male Mice Exposed to Low Dose-Rate Ionizing Radiation

2021 ◽  
Vol 22 (22) ◽  
pp. 12437
Author(s):  
Keiji Ogura ◽  
Yoshiko Ayabe ◽  
Chihiro Harada ◽  
Ignacia Braga Tanaka ◽  
Satoshi Tanaka ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Dose Rate ◽  
Copy Number ◽  
Array Comparative Genomic Hybridization ◽  
Low Dose ◽  
De Novo ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Male Mice ◽  
Low Dose Rate

There is very little information on the transgenerational or genetic effects of low dose-rate ionizing radiation. We report the detection of the transgenerational effects of chronic low dose-rate irradiation in mice, at the molecular level in the whole genome, using array comparative genomic hybridization technology. We observed that the number of the mice with de novo copy number variations (specifically, deletions) was significantly increased in the offspring of C57BL/6J male mice exposed to 20 mGy/day gamma-rays for 400 days (total dose: 8000 mGy), as compared to non-irradiated controls. We did not detect any difference in the size of the de novo deletions between the irradiated and the non-irradiated groups. An analysis of the life span of the offspring suggested a possibility that de novo copy-number variations may be associated with shorter life spans.

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 Heterozygous defects in PAX6 gene and congenital hypopituitarism

2015 ◽  
Vol 172 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Masaki Takagi ◽  
Keisuke Nagasaki ◽  
Ikuma Fujiwara ◽  
Tomohiro Ishii ◽  
Naoko Amano ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
De Novo ◽  
Chromosomal Rearrangements ◽  
Copy Number Variations ◽  
Hormone Deficiency ◽  
Comparative Genomic ◽  
Pituitary Hormone ◽  
Pax6 Gene ◽  
Pituitary Development ◽  
Congenital Hypopituitarism

BackgroundThe prevalence of congenital hypopituitarism (CH) attributable to known transcription factor mutations appears to be rare and other causative genes for CH remain to be identified. Due to the sporadic occurrence of CH, de novo chromosomal rearrangements could be one of the molecular mechanisms participating in its etiology, especially in syndromic cases.ObjectiveTo identify the role of copy number variations (CNVs) in the etiology of CH and to identify novel genes implicated in CH.Subjects and methodsWe enrolled 88 (syndromic: 30; non-syndromic: 58) Japanese CH patients. We performed an array comparative genomic hybridization screening in the 30 syndromic CH patients. For all the 88 patients, we analyzed PAX6 by PCR-based sequencing.ResultsWe identified one heterozygous 310-kb deletion of the PAX6 enhancer region in one patient showing isolated GH deficiency (IGHD), cleft palate, and optic disc cupping. We also identified one heterozygous 6.5-Mb deletion encompassing OTX2 in a patient with bilateral anophthalmia and multiple pituitary hormone deficiency. We identified a novel PAX6 mutation, namely p.N116S in one non-syndromic CH patient showing IGHD. The p.N116S PAX6 was associated with an impairment of the transactivation capacities of the PAX6-binding elements.ConclusionsThis study showed that heterozygous PAX6 mutations are associated with CH patients. PAX6 mutations may be associated with diverse clinical features ranging from severely impaired ocular and pituitary development to apparently normal phenotype. Overall, this study identified causative CNVs with a possible role in the etiology of CH in <10% of syndromic CH patients.

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 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.

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