CNTNAP2 gene polymorphisms in autism spectrum disorder and language impairment among Bangladeshi children: a case–control study combined with a meta-analysis

Uddin, Mohammad Sarowar; Azima, Atkia; Aziz, Abdul; Aka, Tutun Das; Jafrin, Sarah; Millat, Md. Shalahuddin; Siddiqui, Shafayet Ahmed; Uddin, Md. Giash; Hussain, Md. Saddam; Islam, Mohammad Safiqul

doi:10.1007/s13577-021-00546-8

Cited by 14 publications

(12 citation statements)

References 49 publications

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“…The risk allele was different from that for language impairment. In contrast to our results, the G-allele has been observed to be associated with language impairment in children with AD [ 28 ], as well as specific language impairment [ 19 ], and in the general population [ 17 ]. Our results thus extend those previous findings in two meaningful ways: (i) The effect of this SNP in rs2710102 on brain function is not only limited to language skills in TD children, but also extends to intelligence and autistic traits.…”

Section: Discussioncontrasting

confidence: 99%

“…Considering the association between CNTNAP2 and intellectual disabilities, one might infer that rs2710102 itself is related to intelligence. Supporting this hypothesis, Uddin et al recently conducted a case-control study followed by a meta-analysis and concluded that the presence of the G-allele of rs2710102 is associated with language impairment in children with and without ASD [ 28 ]. Similarly, the G-allele was associated with lower language skills in individuals with specific language impairment [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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A common variant of CNTNAP2 is associated with sub-threshold autistic traits and intellectual disability

et al. 2021

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Sub-threshold autistic traits are common in the general population. Children with sub-threshold autistic traits have difficulties with social adaptation. Contactin-associated protein-like 2 (CNTNAP2) is associated with the development of Autism spectrum disorder (ASD) and the single-nucleotide polymorphism rs2710102 (G/A) of CNTNAP2 is suggested to contribute to sub-threshold social impairments and intellectual disabilities. We recruited 67 children with Autistic disorder (AD) (49 boys, 18 girls, aged 38–98 months) and 57 typically developing (TD) children (34 boys, 23 girls, aged 53–90 months). We assessed the participants’ intelligence and social reciprocity using the Kaufman Assessment Battery for Children (K-ABC) and the Social Responsiveness Scale (SRS), respectively. Genomic DNA was extracted from the buccal mucosa and genotyped for rs2710102. A chi-square test revealed a significant association between genotype and group [χ2(2) = 6.56, p = 0.038]. When a co-dominant model was assumed, the results from linear regression models demonstrated that TD children with A-carriers (AA + AG) presented higher SRS T-scores [t(55) = 2.11, p = 0.039] and lower simultaneous processing scale scores of K-ABC [t(55) = -2.19, p = 0.032] than those with GG homozygotes. These associations were not significant in children with ASD. TD children with the rs2710102 A-allele may have more sub-threshold autistic traits than those with GG homozygotes, reflected in higher SRS scores and lower simultaneous processing scale scores. These results support the use of genetic evidence to detect sub-threshold autistic traits.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A common variant of CNTNAP2 is associated with sub-threshold autistic traits and intellectual disability

et al. 2021

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“…Although CNTNAP2 has been proposed to be implicated in ASD [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ], recent studies with large datasets suggest a neutral or less penetrant role for genetic variants of this gene in ASD [ 27 , 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…Besides a number of predisposing factors as mentioned before, genetics has been strongly implicated in the pathophysiology of ASD. In this regard, mutations in genes such as contactin associated protein like 2 gene ( CNTNAP2 ) have been associated with ASD [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. CNTNAP2 , which codes for the neurexin CASPR2, plays a crucial role in the development of the nervous system, in synaptic functions, and neurotransmission [ 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…CNTNAP2 , which codes for the neurexin CASPR2, plays a crucial role in the development of the nervous system, in synaptic functions, and neurotransmission [ 24 , 25 , 26 ]. Although studies have suggested association or predisposition to ASD in individuals with CNTNAP2 mutations [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ], the role of CNTNAP2 in the pathophysiology of autism is still not clear. Studies have reported conflicting results regarding the association of CNTNAP2 with ASD [ 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

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Altered Blood Brain Barrier Permeability and Oxidative Stress in Cntnap2 Knockout Rat Model

Memis

Mittal

Furar

et al. 2022

JCM

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by three core symptoms, specifically impaired social behavior, stereotypic/repetitive behaviors, and sensory/communication deficits. Although the exact pathophysiology of ASD is still unknown, host genetics, oxidative stress, and compromised blood brain barrier (BBB) have been implicated in predisposition to ASD. With regards to genetics, mutations in the genes such as CNTNAP2 have been associated with increased susceptibility of developing ASD. Although some studies observed conflicting results suggesting no association of CNTNAP2 with ASD, other investigations correlated this gene with autism. In addition, CNTNAP2 mediated signaling is generally considered to play a role in neurological disorders due to its critical role in neurodevelopment, neurotransmission, and synaptic plasticity. In this investigation, we studied BBB integrity and oxidative stress in Cntnap2−/− rats. We observed that the BBB permeability was significantly increased in Cntnap2−/− rats compared to littermate wild-type (WT) animals as determined by FITC-dextran and Evans blue assay. High levels of thiobarbituric acid reactive substances and lower amounts of reduced glutathione were observed in brain homogenates of Cntnap2−/− rats, suggesting oxidative stress. Brain sections from Cntnap2−/− rats showed intense inducible nitric oxide synthase immunostaining, which was undetectable in WT animals. Quantification of nitric oxide in brain homogenates revealed significantly high levels in Cntnap2−/− rats compared to the control group. As increased permeability of the BBB and oxidative stress have been observed in ASD individuals, our results suggest that Cntnap2−/− rats have a high construct and face validity and can be explored to develop effective therapeutic modalities.

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A common genetic variant in the Neurexin family member CNTNAP2 is related to language but not communication skills in youth with Autism Spectrum Disorder

Arutiunian,

Santhosh,

Neuhaus

et al. 2024

Autism Research

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One of the candidate genes related to language variability in individuals with Autism Spectrum Disorder (ASD) is the contactin‐associated protein‐like 2 gene (CNTNAP2), a member of the Neurexin family. However, due to the different assessment tools used, it is unknown whether the polymorphisms of the CNTNAP2 gene are linked to structural language skills or more general communication abilities. A total of 302 youth aged 7 to 18 years participated in the present study: 131 verbal youth with ASD (62 female), 130 typically developing (TD) youth (64 female), and 41 unaffected siblings (US) of youth with ASD (25 female). Blood samples were collected to obtain genomic DNA and processed by the Rutgers University Cell and Data Repository or using standard protocols (Gentra Puregene Blood DNA extraction kit; Qiagen). Language and verbal communication skills were screened with the Clinical Evaluation of Language Fundamental‐4 (CELF‐4) and Vineland‐II Communication domain, subsequently. The results showed that the polymorphism of CNTNAP2 (SNP rs2710102) was related to structural language abilities, such that participants carrying the A‐allele had lower language skills in comparison to the G‐allele homozygotes. No relationship was found between the polymorphism of CNTNAP2 and more general communication abilities. Although the study revealed genetic mechanisms that are associated with CELF‐4 measures but not Vineland‐II in youth with ASD, follow‐up studies are needed that will include measures of language and communication that are less correlated to each other as well as will include a group of minimally and/or non‐verbal individuals with ASD.

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CNTNAP2 gene polymorphisms in autism spectrum disorder and language impairment among Bangladeshi children: a case–control study combined with a meta-analysis

Cited by 14 publications

References 49 publications

A common variant of CNTNAP2 is associated with sub-threshold autistic traits and intellectual disability

A common variant of CNTNAP2 is associated with sub-threshold autistic traits and intellectual disability

Altered Blood Brain Barrier Permeability and Oxidative Stress in Cntnap2 Knockout Rat Model

A common genetic variant in the Neurexin family member CNTNAP2 is related to language but not communication skills in youth with Autism Spectrum Disorder

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