{"i":"TBR1","#text":"Novelc.1303C>T Variant Led to Diagnosis of Intellectual Developmental Disorder with Autism and Speech Delay: Application of Comprehensive Family-Based Whole-Genome Analysis."}

Researchers studied a 7-year-old girl with autism features and speech delays. They found a new genetic change in the TBR1 gene that wasn't present in her parents. This genetic change causes a rare condition called IDDAS, which involves intellectual disability, speech problems, and autism features. This is the first time this specific genetic change has been reported, helping doctors better understand this rare condition.

This case report describes a 7-year-old female with intellectual developmental disorder with autism and speech delay (IDDAS) caused by a novel genetic variant. Using whole-genome sequencing of the child and both parents (trio analysis), researchers identified a previously unreported nonsense variant (c.1303C>T) in the TBR1 gene that occurred de novo (not inherited from parents). The variant creates a premature stop codon, likely disrupting normal protein function. IDDAS is a rare neurological condition characterized by intellectual disability, speech delays, and autism spectrum features, genetically linked to TBR1 gene variants.

This represents the first reported case of this specific variant causing IDDAS, contributing to understanding of the genetic spectrum underlying this rare syndrome.

This case expands genetic testing considerations for children presenting with combined intellectual disability, autism features, and speech delays. The identification of novel TBR1 variants supports comprehensive genomic testing in similar presentations and contributes to genetic counseling resources for families affected by IDDAS.

Single case report limits generalizability. No functional studies provided to confirm variant pathogenicity. Long-term outcomes and treatment responses not described. Sample size of one prevents broader conclusions about variant frequency or phenotypic spectrum.

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 thegene. 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. The joint-genome analysis identified a novel NM_006593.4():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. This is the first report of the NM_006593.4():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.