Early infantile ‐onset epileptic encephalopathy 28 due to a homozygous microdeletion involving the WWOX gene in a region of uniparental disomy

This report describes a rare autosomal recessive disorder with multiple genetic etiologies, one that involves uniparental disomy. A 6 ‐year‐old girl was admitted to the NIH Undiagnosed Diseases Program with profound intellectual disability, infantile‐onset seizures, facial dysmorphisms, and skeletal abnormalities. Chromosome 16q22.1–16q24.3 uniparental disomy, included a maternally inherited homozygous microdeletion coveri ng exon 6 ofWWOX (NM_016373.3), which could cause the seizures and intellectual disability. Additional pathogenic compound heterozygous variants inHSPG2 are likely responsible for the patient's skeletal abnormalities. AbstractThe genetic etiologies of many rare disorders, including early infantile epileptic encephalopathies, are largely undiagnosed. A 6 ‐year‐old girl was admitted to the National Institutes of Health Undiagnosed Diseases Program with profound intellectual disability, infantile‐onset seizures, chronic respiratory failure, facial dysmorphisms, skeletal abnormalities, and atrial septum defect. A large region of homozygosity was discovered on chromosome 16, spanning 16q22.1–16q24.3' caused by uniparental disomy (UPD) that included a maternally inherited homozygous microdeletion covering exon 6 ofWWOX (NM_016373.3). mRNA expression analysis revealed that the deletion led to nonsense ‐mediated decay of the NM_016373.3 transcript; the exon 6 of an alternative transcript (NM_130791.3), lacking the short‐chain dehydrogenase, was ...
Source: Human Mutation - Category: Genetics & Stem Cells Authors: Tags: BRIEF REPORT Source Type: research