Novel TBR1 c.1303C>T Variant Led to Diagnosis of Intellectual Developmental Disorder with Autism and Speech Delay: Application of Comprehensive Family-Based Whole-Genome Analysis
Copyright policy )Novel TBR1 c.1303C>T Variant Led to Diagnosis of Intellectual Developmental Disorder with Autism and Speech Delay: Application of Comprehensive Family-Based Whole-Genome Analysis
Background: Intellectual developmental disorder with autism and speech delay (IDDAS) is a rare and complex neurological disorder characterized by the presence of both intellectual and speech impairment and features of autism spectrum disorder (ASD). The prevalence of IDDAS is unknown but genetically, it is caused by heterozygous variants in the TBR1 gene. Methods: A 7-year-old female with autistic features and delayed speech development was presented with unaffected parents. Trio-joint analysis was conducted on whole-genome sequencing (WGS) data from the proband and unaffected parents. A phenotype-driven analysis was conducted to investigate variants related to the patient’s clinical presentation. A zygosity-focused analysis was performed to investigate de novo and compound heterozygote variants related to the etiology. Results: The joint-genome analysis identified a novel NM_006593.4(TBR1):c.1303C>T p.Gln435* nonsense variant in the proband. The de novo analysis confirmed the absence of the variant in the parents. No additional causative variants were identified in genes associated with the proband’s phenotype. Conclusions: This is the first report of the NM_006593.4(TBR1):c.1303C>T variant in a patient with IDDAS. This study presents the clinical features of the patient and highlights details of trio-WGS analysis in the molecular diagnosis of this complex disease. Sharing these details is important, as they contribute to the understanding of the spectrum of this rare syndrome.
- Brigham and Women's Faulkner Hospital United States
- Harvard University United States
- University Hospital Centre Zagreb Croatia
- University of Zagreb Croatia
- Brigham and Women's Hospital United States
Whole Genome Sequencing, Autism Spectrum Disorder, Brief Report, Language Development Disorders / diagnosis, T-Box Domain Proteins / genetics, Autistic Disorder / diagnosis, Autistic Disorder / genetics, Pedigree, Phenotype, Autism Spectrum Disorder / genetics, Intellectual Disability, Humans, Female, Language Development Disorders, Autistic Disorder, Child, T-Box Domain Proteins, Intellectual Disability / genetics, Intellectual Disability / diagnosis, Language Development Disorders / genetics
Whole Genome Sequencing, Autism Spectrum Disorder, Brief Report, Language Development Disorders / diagnosis, T-Box Domain Proteins / genetics, Autistic Disorder / diagnosis, Autistic Disorder / genetics, Pedigree, Phenotype, Autism Spectrum Disorder / genetics, Intellectual Disability, Humans, Female, Language Development Disorders, Autistic Disorder, Child, T-Box Domain Proteins, Intellectual Disability / genetics, Intellectual Disability / diagnosis, Language Development Disorders / genetics
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