Whole-Exome Sequencing Identified a Novel DYRK1A Variant in a Patient With Intellectual Developmental Disorder,...

Area of Science:

• Genetics
• Rare Diseases
• Clinical Diagnostics

Background:

• Intellectual developmental disorder, autosomal dominant 7 (MRD7) is a rare genetic disorder.
• It is characterized by microcephaly, intellectual disability, speech delay, feeding difficulties, and facial dysmorphisms.
• Pathogenic variants in the DYRK1A gene cause MRD7.

Observation:

• A 22-year-old male patient with microcephaly, intellectual disability, and facial dysmorphisms was initially diagnosed with Cornelia de Lange syndrome (CdLS).
• The patient's low CdLS score prompted re-evaluation.
• The Face2Gene application suggested MRD7 as a potential diagnosis.

Findings:

• Whole-exome sequencing (WES) and Sanger sequencing identified a novel heterozygous duplication variant (c.848dup, p.(Asn283LysfsTer6)) in the DYRK1A gene.
• This variant introduces a premature stop codon, confirming the MRD7 diagnosis.
• The identified variant expands the known phenotypic spectrum of MRD7 in a young adult.

Implications:

• This case highlights the utility of the Face2Gene application in identifying rare genetic disorders.
• Whole-exome sequencing is a powerful tool for diagnosing rare genetic diseases like MRD7.
• Further registration of genetically confirmed MRD7 cases will enhance diagnostic accuracy in tools like Face2Gene.