Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autism spectrum disorder (ASD) is a group of clinically and genetically heterogeneous neurodevelopmental disorders. Recent tremendous advances in the whole exome sequencing (WES) enable rapid identification of variants associated with ASD including single nucleotide variations (SNVs) and indels. To further explore genetic etiology of ASD in Chinese children with negative findings of copy number variants (CNVs), we applied WES in 80 simplex families with a single affected offspring with ASD or suspected ASD, and validated variations predicted to be damaging by Sanger sequencing. The results showed that an overall diagnostic yield of 8.8% (9.2% in the group of ASD and 6.7% in the group of suspected ASD) was observed in our cohort. Among patients with diagnosed ASD, developmental delay or intellectual disability (DD/ID) was the most common comorbidity with a diagnostic yield of 13.3%, followed by seizures (50.0%) and craniofacial anomalies (40.0%). All of identified de novo SNVs and indels among patients with ASD were loss of function (LOF) variations and were slightly more frequent among female (male vs. female: 7.3% vs. 8.5%). A total of seven presumed causative genes (CHD8, AFF2, ADNP, POGZ, SHANK3, IL1RAPL1, and PTEN) were identified in this study. In conclusion, WES is an efficient diagnostic tool for diagnosed ASD especially those with negative findings of CNVs and other neurological disorders in clinical practice, enabling early identification of disease related genes and contributing to precision and personalized medicine.
 ...
PMID:Genetic Diagnostic Evaluation of Trio-Based Whole Exome Sequencing Among Children With Diagnosed or Suspected Autism Spectrum Disorder. 3055 18

POGZ (# 614787) encodes a multidomain nuclear protein involved in transcriptional regulation and its defective function has been recently associated with a syndromic neurodevelopmental disorder, known as White-Sutton syndrome (# 616364). While originally epileptic seizures were unreported, it seems that epilepsy represents a recurrent feature in affected subjects. Few data, however, are available on electroclinical features of POGZ-related epilepsy. We report a 5-year-old girl with a de novo inactivating POGZ mutation with a complex neurological phenotype characterized by hypotonia, severe developmental delay, and paroxysmal epileptic and nonepileptic events. Comparing this patient with the previously reported nine cases exhibiting epilepsy as associated feature, we detected that epilepsy onset is mostly during infancy (1-4 years of age), with both focal and generalized seizures. EEGs reveal that epileptic abnormalities mainly are localized in the frontal regions, and seizure control might be reached with one or multiple antiepileptic drugs. Besides dysmorphic features and other comorbidities (microcephaly, intellectual disability, absent speech, sensorineural hearing loss, and autistic spectrum disorder) major brain MR features include cortical and cerebellar atrophy, delayed myelination, and brainstem hypoplasia. Although the small number of patients reported, we were able to delineate primary electroclinical epileptic phenotype related to POGZ mutations. This would be crucial for an early identification and management of the condition.
 ...
PMID:POGZ-related epilepsy: Case report and review of the literature. 3113 90