SCN8Asodium channel, voltage gated, type VIII, alpha subunit

Description

Heterozygous mutations in SCN8A are associated with multiple disorders, including early infantile epileptic encephalopathy (OMIM 614558), benign familial infantile seizures (OMIM 617080), and cognitive impairment with or without cerebellar ataxia (OMIM 614306); in some cases, individuals with one of these disorders also present with ASD or autistic features (Larsen et al., 2015). A rare de novo missense variant in the SCN8A gene was found in a patient with epilepsy, autism, intellectual disability and developmental delay in Veeramah et al., 2012; functional analysis of this variant was consistent with a gain-of-function phenotype in this patient, and mice that were heterozygous for this variant (Scn8aN1768D/+) exhibited seizures, SUDEP, and mild impairments in motor coordination and social discrimination (Wagnon et al., 2014). De novo missense variants in SCN8A have been identified in individuals presenting with ASD and intellectual disability in the presence or absence of seizures (Blanchard et al., 2015; Bowling et al., 2017). Potentially damaging missense variants in SCN8A have been identified in ASD probands in several additional studies (Butler et al., 2017; Geisheker et al., 2017; Li et al., 2017).

Description

Heterozygous mutations in SCN8A are associated with multiple disorders, including early infantile epileptic encephalopathy (OMIM 614558), benign familial infantile seizures (OMIM 617080), and cognitive impairment with or without cerebellar ataxia (OMIM 614306); in some cases, individuals with one of these disorders also present with ASD or autistic features (Larsen et al., 2015). A rare de novo missense variant in the SCN8A gene was found in a patient with epilepsy, autism, intellectual disability and developmental delay in Veeramah et al., 2012; functional analysis of this variant was consistent with a gain-of-function phenotype in this patient, and mice that were heterozygous for this variant (Scn8aN1768D/+) exhibited seizures, SUDEP, and mild impairments in motor coordination and social discrimination (Wagnon et al., 2014). De novo missense variants in SCN8A have been identified in individuals presenting with ASD and intellectual disability in the presence or absence of seizures (Blanchard et al., 2015; Bowling et al., 2017). Potentially damaging missense variants in SCN8A have been identified in ASD probands in several additional studies (Butler et al., 2017; Geisheker et al., 2017; Li et al., 2017).

Description

Heterozygous mutations in SCN8A are associated with multiple disorders, including early infantile epileptic encephalopathy (OMIM 614558), benign familial infantile seizures (OMIM 617080), and cognitive impairment with or without cerebellar ataxia (OMIM 614306); in some cases, individuals with one of these disorders also present with ASD or autistic features (Larsen et al., 2015). A rare de novo missense variant in the SCN8A gene was found in a patient with epilepsy, autism, intellectual disability and developmental delay in Veeramah et al., 2012; functional analysis of this variant was consistent with a gain-of-function phenotype in this patient, and mice that were heterozygous for this variant (Scn8aN1768D/+) exhibited seizures, SUDEP, and mild impairments in motor coordination and social discrimination (Wagnon et al., 2014). De novo missense variants in SCN8A have been identified in individuals presenting with ASD and intellectual disability in the presence or absence of seizures (Blanchard et al., 2015; Bowling et al., 2017). Potentially damaging missense variants in SCN8A have been identified in ASD probands in several additional studies (Butler et al., 2017; Geisheker et al., 2017; Li et al., 2017).

Description

Heterozygous mutations in SCN8A are associated with multiple disorders, including early infantile epileptic encephalopathy (OMIM 614558), benign familial infantile seizures (OMIM 617080), and cognitive impairment with or without cerebellar ataxia (OMIM 614306); in some cases, individuals with one of these disorders also present with ASD or autistic features (Larsen et al., 2015). A rare de novo missense variant in the SCN8A gene was found in a patient with epilepsy, autism, intellectual disability and developmental delay in Veeramah et al., 2012; functional analysis of this variant was consistent with a gain-of-function phenotype in this patient, and mice that were heterozygous for this variant (Scn8aN1768D/+) exhibited seizures, SUDEP, and mild impairments in motor coordination and social discrimination (Wagnon et al., 2014). De novo missense variants in SCN8A have been identified in individuals presenting with ASD and intellectual disability in the presence or absence of seizures (Blanchard et al., 2015; Bowling et al., 2017). Potentially damaging missense variants in SCN8A have been identified in ASD probands in several additional studies (Butler et al., 2017; Geisheker et al., 2017; Li et al., 2017).

Description

Heterozygous mutations in SCN8A are associated with multiple disorders, including early infantile epileptic encephalopathy (OMIM 614558), benign familial infantile seizures (OMIM 617080), and cognitive impairment with or without cerebellar ataxia (OMIM 614306); in some cases, individuals with one of these disorders also present with ASD or autistic features (Larsen et al., 2015). A rare de novo missense variant in the SCN8A gene was found in a patient with epilepsy, autism, intellectual disability and developmental delay in Veeramah et al., 2012; functional analysis of this variant was consistent with a gain-of-function phenotype in this patient, and mice that were heterozygous for this variant (Scn8aN1768D/+) exhibited seizures, SUDEP, and mild impairments in motor coordination and social discrimination (Wagnon et al., 2014). De novo missense variants in SCN8A have been identified in individuals presenting with ASD and intellectual disability in the presence or absence of seizures (Blanchard et al., 2015; Bowling et al., 2017). Potentially damaging missense variants in SCN8A have been identified in ASD probands in several additional studies (Butler et al., 2017; Geisheker et al., 2017; Li et al., 2017).

New Scoring Scheme

Description

Heterozygous mutations in SCN8A are associated with multiple disorders, including early infantile epileptic encephalopathy (OMIM 614558), benign familial infantile seizures (OMIM 617080), and cognitive impairment with or without cerebellar ataxia (OMIM 614306); in some cases, individuals with one of these disorders also present with ASD or autistic features (Larsen et al., 2015). A rare de novo missense variant in the SCN8A gene was found in a patient with epilepsy, autism, intellectual disability and developmental delay in Veeramah et al., 2012; functional analysis of this variant was consistent with a gain-of-function phenotype in this patient, and mice that were heterozygous for this variant (Scn8aN1768D/+) exhibited seizures, SUDEP, and mild impairments in motor coordination and social discrimination (Wagnon et al., 2014). De novo missense variants in SCN8A have been identified in individuals presenting with ASD and intellectual disability in the presence or absence of seizures (Blanchard et al., 2015; Bowling et al., 2017). Potentially damaging missense variants in SCN8A have been identified in ASD probands in several additional studies (Butler et al., 2017; Geisheker et al., 2017; Li et al., 2017).

Description

Heterozygous mutations in SCN8A are associated with multiple disorders, including early infantile epileptic encephalopathy (OMIM 614558), benign familial infantile seizures (OMIM 617080), and cognitive impairment with or without cerebellar ataxia (OMIM 614306); in some cases, individuals with one of these disorders also present with ASD or autistic features (Larsen et al., 2015). A rare de novo missense variant in the SCN8A gene was found in a patient with epilepsy, autism, intellectual disability and developmental delay in Veeramah et al., 2012; functional analysis of this variant was consistent with a gain-of-function phenotype in this patient, and mice that were heterozygous for this variant (Scn8aN1768D/+) exhibited seizures, SUDEP, and mild impairments in motor coordination and social discrimination (Wagnon et al., 2014). De novo missense variants in SCN8A have been identified in individuals presenting with ASD and intellectual disability in the presence or absence of seizures (Blanchard et al., 2015; Bowling et al., 2017). Potentially damaging missense variants in SCN8A have been identified in ASD probands in several additional studies (Butler et al., 2017; Geisheker et al., 2017; Li et al., 2017).

Description

Heterozygous mutations in SCN8A are associated with multiple disorders, including early infantile epileptic encephalopathy (OMIM 614558), benign familial infantile seizures (OMIM 617080), and cognitive impairment with or without cerebellar ataxia (OMIM 614306); in some cases, individuals with one of these disorders also present with ASD or autistic features (Larsen et al., 2015). A rare de novo missense variant in the SCN8A gene was found in a patient with epilepsy, autism, intellectual disability and developmental delay in Veeramah et al., 2012; functional analysis of this variant was consistent with a gain-of-function phenotype in this patient, and mice that were heterozygous for this variant (Scn8aN1768D/+) exhibited seizures, SUDEP, and mild impairments in motor coordination and social discrimination (Wagnon et al., 2014). De novo missense variants in SCN8A have been identified in individuals presenting with ASD and intellectual disability in the presence or absence of seizures (Blanchard et al., 2015; Bowling et al., 2017). Potentially damaging missense variants in SCN8A have been identified in ASD probands in several additional studies (Butler et al., 2017; Geisheker et al., 2017; Li et al., 2017).

Description

Heterozygous mutations in SCN8A are associated with multiple disorders, including early infantile epileptic encephalopathy (OMIM 614558), benign familial infantile seizures (OMIM 617080), and cognitive impairment with or without cerebellar ataxia (OMIM 614306); in some cases, individuals with one of these disorders also present with ASD or autistic features (Larsen et al., 2015). A rare de novo missense variant in the SCN8A gene was found in a patient with epilepsy, autism, intellectual disability and developmental delay in Veeramah et al., 2012; functional analysis of this variant was consistent with a gain-of-function phenotype in this patient, and mice that were heterozygous for this variant (Scn8aN1768D/+) exhibited seizures, SUDEP, and mild impairments in motor coordination and social discrimination (Wagnon et al., 2014). De novo missense variants in SCN8A have been identified in individuals presenting with ASD and intellectual disability in the presence or absence of seizures (Blanchard et al., 2015; Bowling et al., 2017). Potentially damaging missense variants in SCN8A have been identified in ASD probands in several additional studies (Butler et al., 2017; Geisheker et al., 2017; Li et al., 2017).

Description

Heterozygous mutations in SCN8A are associated with multiple disorders, including early infantile epileptic encephalopathy (OMIM 614558), benign familial infantile seizures (OMIM 617080), and cognitive impairment with or without cerebellar ataxia (OMIM 614306); in some cases, individuals with one of these disorders also present with ASD. A rare de novo missense variant in the SCN8A gene was found in a patient with epilepsy, autism, intellectual disability and developmental delay in Veeramah et al., 2012; functional analysis of this variant was consistent with a gain-of-function phenotype in this patient, and mice that were heterozygous for this variant (Scn8aN1768D/+) exhibited seizures, SUDEP, and mild impairments in motor coordination and social discrimination (Wagnon et al., 2014). De novo missense variants in SCN8A have been identified in individuals presenting with ASD and intellectual disability in the presence or absence of seizures (Blanchard et al., 2015; Bowling et al., 2017). Potentially damaging missense variants in SCN8A have been identified in ASD probands in several additional studies (Butler et al., 2017; Geisheker et al., 2017; Li et al., 2017).