Cureus, Whole-Exome Sequencing Identified a Novel DYRK1A Variant in a Patient With Intellectual Developmental Disorder, Autosomal Dominant 7

Intellectual developmental disorder, autosomal dominant 7 (MRD7; OMIM 614104) is a rare disease characterized by microcephaly, intellectual disability, speech delay, feeding difficulties, and facial dysmorphisms. This disorder is caused by pathogenic/likely pathogenic variants of the DYRK1A gene, which encodes dual-specificity tyrosine-phosphorylation-regulated kinase 1A. Here, we report a case of MRD7 that was diagnosed using Face2Gene and whole-exome sequencing (WES). A 22-year-old man presented with microcephaly, intellectual disability, slender body, long slender fingers, and facial dysmorphisms. He was previously diagnosed with Cornelia de Lange syndrome (CdLS) at four years of age. However, his CdLS clinical diagnostic score was low at 22 years of age. The Face2Gene application introduced several candidate diseases including MRD7. Finally, by utilizing WES and Sanger sequencing analysis of cloned cDNA, we identified a novel heterozygous duplication variant (c.848dup, p.(Asn283LysfsTer6)) in the DYRK1A gene, which introduces a premature stop codon. This report provides more information about the phenotypic spectrum of a young adult patient with MRD7. Face2Gene helped us introduce candidate diseases of the patient. Registering further genetically confirmed cases with MRD7 will improve the accuracy of the diagnostic recommendations in Face2Gene. Moreover, WES is a powerful tool for diagnosing rare genetic diseases, such as MRD7.

Expanding the Genotypic Spectrum of Congenital Sensory and Autonomic Neuropathies Using Whole-Exome Sequencing

Publications using Face2Gene - Face2Gene

A novel UBE2A splice site variant causing intellectual disability type Nascimento - Yan - 2022 - Clinical Case Reports - Wiley Online Library

Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders

Autosomal recessive mutations in THOC6 cause intellectual disability: syndrome delineation requiring forward and reverse phenotyping - Amos - 2017 - Clinical Genetics - Wiley Online Library

Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders

Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders

Whole exome sequencing reveals putatively novel associations in retinopathies and drusen formation

Publications using Face2Gene - Face2Gene

Whole-exome sequencing reveals a novel homozygous mutation in the COQ8B gene associated with nephrotic syndrome

The role of de novo mutations in adult-onset neurodegenerative disorders

DYRK1A pathogenic variants in two patients with syndromic intellectual disability and a review of the literature. - Abstract - Europe PMC