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Abstract Intellectual disabilities (ID) are etiologically heterogeneous. Advanced molecular techniques could be helpful in identification of the underlying genetic defects. We aimed to characterize clinical and molecular features of three Thai patients with ID. Patient 1 had ID, hypotonia and lactic acidosis. Patient 2 had ID and growth failure. Patient 3 had ID, seizure, diarrhea and hypoglycemia. Whole exome sequencing found that Patient 1 was homozygous for a nonsense, c.1303C>T (p.Arg435Ter), mutation in FBXL4 , a gene responsible for encephalomyopathic mitochondrial DNA depletion syndrome-13 (MTDPS13). Patient 2 was compound heterozygous for two novel mutations, c.3226C>T (p.Arg1076Ter) and c.3205C>T (p.Arg1069Ter), in UNC80 , a known gene of infantile hypotonia with psychomotor retardation and characteristic facies-2 (IHPRF2). Patient 3 was homozygous for a novel missense, c.427T>C (p.Cys143Arg), mutation in ADK , a known gene of adenosine kinase deficiency leading to hypermethioninemia. This study expands the mutational spectra of ID genes. Highlights • Novel mutations in intellectual disability genes are found, expanding the mutational spectrum. • Patients with biallelic nonsense mutations in FBXL4 are associated with more severe clinical presentation and shorter lifespan than those with missenses. • Since ID is extremely etiologically heterogeneous, we propose whole exome sequencing as the first diagnostic step for these patients. [ABSTRACT FROM AUTHOR]

• Pathogenic variants in ATP1A3 are known to be associated with three distinct neurological syndromes including AHC, RDP and CAPOS. • This study suggests the broader diversity of ATP1A3 -related disorders. • Atypical features were observed in two patients expanding the phenotypic spectrum of ATP1A3 -related disorders. • Three novel causative variants were identified expanding the genotypic spectrum of ATP1A3. Mutations in the ATP1A3 gene are known to be the cause of three distinct neurological syndromes including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP) and cerebellar ataxia, arefexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS). Recent studies have suggested the broader diversity of ATP1A3- related disorders. This study aimed to investigate the clinical spectrum in patients carrying causative mutations within the ATP1A3 gene. The medical histories of nine unrelated patients with diverse phenotypes harboring variants in ATP1A3 were retrospectively analyzed after they were referred to a tertiary epilepsy center in one of the two different health care systems (Germany or Thailand). Clinical features, neurophysiological data, imaging results, genetic characteristics and treatments were reviewed. Three patients harbor novel mutations in the ATP1A3 gene. Atypical clinical features and imaging findings were observed in two cases, one with hemiplegia-hemiconvulsion-epilepsy syndrome, and the other with neurodegeneration with brain iron accumulation. All nine patients presented with intellectual impairment. Alternating hemiplegia of childhood (AHC) was the most common phenotype (67%). Flunarizine and topiramate led to symptom reduction in 83% and 25% of AHC cases administered, respectively. The present case series expands the clinical and genetic spectrum of ATP1A3 -related disorders. [ABSTRACT FROM AUTHOR]