Chromosome 15q11-q13 copy number gain detected by array-CGH in two cases with a maternal methylation pattern

Tan, Ee‐Shien; Yong, Ming Hui; Lim, Eileen C.P.; Li, Zhihui; Brett, Maggie; Tan, Ene‐Choo

doi:10.1186/1755-8166-7-32

Cited by 8 publications

(7 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to Tan et al . [ 36 ], at least three genes ( NIPA1 , NIPA2 , CYFIP1 ), located in this region were associated with the development of CNS (central nervous system). A duplication of the copy of the SNRPN gene obtained from the mother is associated with autism.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Benign, pathogenic and copy number variations of unknown clinical significance in patients with congenital malformations and developmental delay

Mihaylova

Staneva

Toncheva

et al. 2017

Balkan Journal of Medical Genetics

View full text Add to dashboard Cite

The high frequency (3.0-5.0%) of congenital anomalies (CA) and intellectual disabilities (IDs), make them a serious problem, responsible for a high percentage (33.0%) of neonatal mortality. The genetic cause remains unclear in 40.0% of cases. Recently, molecular karyotyping has become the most powerful method for detection of pathogenic imbalances in patients with multiple CAs and IDs. This method is with high resolution and gives us the opportunity to investigate and identify candidate genes that could explain the genotype-phenotype correlations. This article describes the results from analysis of 81 patients with congenital malformations (CMs), developmental delay (DD) and ID, in which we utilized the CytoChip ISCA oligo microarray, 4 × 44 k, covering the whole genome with a resolution of 70 kb. In the selected group of patients with CAs, 280 copy number variations (CNVs) have been proven, 41 were pathogenic, 118 benign and 121 of unknown clinical significance (average number of variations 3.5). In six patients with established pathogenic variations, our data revealed eight pathogenic aberrations associated with the corresponding phenotype. The interpretation of the other CNVs was made on the basis of their frequency in the investigated group, the size of the variation, content of genes in the region and the type of the CNVs (deletion or duplication).

show abstract

Section: Discussionmentioning

confidence: 99%

“…Other important genes associated with the development and neurological disorders are GABRA5 , GABRA3 , GABRG3 , MAGEL2 , MKRN3 , NDN , SNRPN and UBE3A . The first three encode subunits of the GABA-receptors that mediate the main inhibitory neurotransmitter in the brain (GABA) [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Benign, pathogenic and copy number variations of unknown clinical significance in patients with congenital malformations and developmental delay

Mihaylova

Staneva

Toncheva

et al. 2017

Balkan Journal of Medical Genetics

View full text Add to dashboard Cite

show abstract

“…Chromosome 15 is reportedly the most common site of autosomal abnormalities in autism with the duplication of 15q11-q13 being the most frequently reported alteration. This region contains at least 30 genes, several of which have been associated to ASD, neurobehavioral disorders, cognitive deficits, hypotonia, language delay and seizures [141,154].This region, known for its genetic instability, contains many low copy repeats and segmental duplications. It is known as a critical region for Prader-Willi/Angelman syndrome and has a complex pattern of paternal and maternal imprinting; it contains at least five paternally expressed genes (MKRN3, MAGEL2, NDN, C15orf2, snoRNAs and SNRPN-SNURF) and two maternally expressed genes (UBE3A and ATP10A).…”

Section: Common Chromosomal Alterations: 15q11-q13 16p112 and 22q112mentioning

confidence: 99%

Etiology of Autism the Complexity of Risk Factors in Autism Spectrum Disorder

Fett‐Conte¹,

Bossolani-Martins²,

Rosan³

2015

Autism Spectrum Disorder - Recent Advances

View full text Add to dashboard Cite

Additional information is available at the end of the chapter http://dx.doi.org/10.5772/59109. Introduction "utism Spectrum Disorder "SD , also currently known as autism, refers to a group of complex behavioral disorders of varying severity, characterized by manifestations noted in early childhood, usually before the age of three and defined as impaired social communication and presence of restricted interests and repetitive behaviors, compromising the entire life of the individual DSM-. The etiology is very complex and heterogeneous, with numerous causes described, and includes genetic, epigenetic, or environmental factors in isolation or associated. It aggregates in families with the heritability being estimated at . , but the individual risk and to what extent this is caused by genetic factors or environmental factors remains unresolved. These factors probably interact at least in the majority of cases, and thus the assessment of individuals and genetic counseling is further complicated [ ].Valuable information is been gained through the identification of candidate genes, though case-control and association studies and more recently by comparative genomic hybridization and whole exome and genome sequencing. In the epigenetic area, mechanisms such as genomic imprinting, epimutations and methylation have been identified [ ]. Copy number variations CNVs have gained prominence on the stage of the discovery of the causes of autism. The de novo CNVs have been reported in % of simplex families and ~ % in multiplex families. Moreover, hypomorphic alterations in some genes suggest oligogenic inheritance. Recently, discoveries employing large-scale whole exome sequencing WES showed that one gene alone is not able to confer significant risk for autism. Instead, the most probable hypothesis is the contribution of several risk variants that are scattered in hundreds of genes. There are approximately , genes involved in molecular pathways, gene regulation and functional domains that may contribute to neurodevelopmental disorders. It is noteworthy that the same genes can cause different disorders leading to an etiologic overlap [ ].One other issue that has emerged recently is that a significant number of synaptic proteins directly or indirectly affect the structure and function of neurons, dendrites and synapses. Subtle changes in the dendritic and synaptic structures can lead to huge changes in information processing. Dendritic branches and spines are essential for the formation and plasticity of neuronal circuits but are interrupted in many neurologic disorders, such as autism. In many cases the same mutations are observed in unaffected relatives. This suggests the existence of a compensatory mechanism or other genetic or non-genetic causes [ ].New findings on the genetic etiology of autism have pointed to the participation of regulatory regions of transcription factors, the microRN"s miRN"s , a class of noncoding RN"s of ~ nucleotides that suppress translation by pairing with miRN" recognition elements present in the 'un...

show abstract

“…In particular, the most frequent site of autosomal anomalies in ASD is chromosome 15, with the duplication of 15q11-q13 being the most encountered alteration. Interestingly, this region contains about 30 genes, most of which are highly associated with ASD, neurobehavioral disorders, cognitive deficits, hypotonia and seizures [9,10]. The second most common abnormality in ASD is a phenotypic microdeletions and microduplications in the 16p11.2, which entails incomplete symptoms of variable expressivity and neurodevelopmental impairments including intellectual disability and epilepsy on top of autism.…”

Section: Introduction and Challenges Posed By Autismmentioning

confidence: 99%

Emerging Clues and Altered Metabolic Findings in Autism: Breakthroughs and Prospects from Omics Studies

Mowafy¹

2016

Autism Open Access

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is a pervasive broad-spectrum disorder that involves multifaceted delays in the development of many basic, social, and communication skills. The etiology of ASD is multifactorial and involves interplay among genetic, neurologic, hormonal, metabolic, immune-inflammatory, and environmental factors; which further complicate both the diagnosis and management in affected individuals. This review delineates the underpinnings of clinical challenges posed by ASD, like clinical heterogeneity of patient presentation, unresolved ASD genomic map and deficient drug therapy. Besides, it addresses the emerging pathogenic, etiologic, and diagnostic clues of diverse origins, encompassing genetic-, neurotransmitter-, androgenic-and immunoinflammatory-anomalies in ASD patients, as availed by advances in Omics technologies (like genomics and proteomics). Moreover, as unravelled by metabolomics studies, metabolic flaws that pertain to amino acids, fatty acids, mitochondrial anomalies, and oxidative-stress are highlighted and further correlated with the extent of clinical picture and malbehaviors coherent with ASD patients. Lastly, future directions are underlined to promote and rationalize ASD research so as to help translate its findings into remedy.

show abstract

Chromosome 15q11-q13 copy number gain detected by array-CGH in two cases with a maternal methylation pattern

Cited by 8 publications

References 36 publications

Benign, pathogenic and copy number variations of unknown clinical significance in patients with congenital malformations and developmental delay

Benign, pathogenic and copy number variations of unknown clinical significance in patients with congenital malformations and developmental delay

Etiology of Autism the Complexity of Risk Factors in Autism Spectrum Disorder

Emerging Clues and Altered Metabolic Findings in Autism: Breakthroughs and Prospects from Omics Studies

Contact Info

Product

Resources

About