Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000187221 | SCV000240803 | uncertain significance | not provided | 2012-08-09 | criteria provided, single submitter | clinical testing | p.Gly977Val (GGA>GTA):c.2930 G>T in exon 18 of the CNTNAP2 gene (NM_014141.4). Mutations in CNTNAP2 cause autosomal recessive Pitt-Hopkins-like syndrome, which is characterized by intellectual disability, autism, early-onset epilepsy, dysmorphology, breathing abnormalities, and schizophrenia (Zweier et al., 2009; Gregor et al., 2011; Bakkaloglu et al., 2008). Additionally, a founder mutation (c.3709delG) in the Amish population causes a distinct autosomal recessive disorder resulting in cortical dysplasia and early-onset intractable focal epilepsy (Strauss et al., 2006). In families with autosomal recessive CNTNAP2-related disorders, heterozygous carriers have been reported to be unaffected (Strauss et al., 2006; Zweier et al., 2009). However, in other studies heterozygous mutations and deletions of CNTNAP2 have been reported to confer susceptibility to neuropsychiatric disorders, including intellectual disability, epilepsy, autism, and schizophrenia (Mikhail et al., 2011; O'Roak et al., 2011; Friedman et al., 2008; Bakkaloglu et al., 2008). These heterozygous variants may be inherited from an unaffected parent, indicating incomplete penetrance and providing evidence that additional genetic and/or environmental factors influence the phenotype (Elia et al., 2010; Gregor et al., 2011; Bakkaloglu et al., 2008; O'Roak et al., 2011; Mefford et al., 2010; Poot et al., 2010). CNTNAP2-related disorders are clinically variable, even among affected individuals within the same families (Zweier et al., 2009; Bakkaloglu et al., 2009). The variant is found in EPILEPSY panel(s). |