Sustained therapeutic response to riboflavin in a child with a progressive neurological condition, diagnosed by whole-exome sequencing.

One of the most promising outcomes of whole-exome sequencing (WES) is the alteration of medical management following an accurate diagnosis in patients with previously unresolved disorders. Although case reports of targeted therapies resulting from WES have been published, there are few reports with long-term follow-up that confirm a sustained therapeutic response. Following a diagnosis by WES of Brown-Vialetto-Van Laere Syndrome 2 (BVVLS2), high-dose riboflavin therapy was instituted in a 20-mo-old child.

Exome sequencing results in successful riboflavin treatment of a rapidly progressive neurological condition.

Genetically targeted therapies for rare Mendelian conditions are improving patient outcomes. Here, we present the case of a 20-mo-old female suffering from a rapidly progressing neurological disorder. Although diagnosed initially with a possible autoimmune condition, analysis of the child's exome resulted in a diagnosis of Brown-Vialetto-Van Laere syndrome 2 (BVVLS2).

Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway.

Purpose: The endoplasmic reticulum-associated degradation pathway is responsible for the translocation of misfolded proteins across the endoplasmic reticulum membrane into the cytosol for subsequent degradation by the proteasome. To define the phenotype associated with a novel inherited disorder of cytosolic endoplasmic reticulum-associated degradation pathway dysfunction, we studied a series of eight patients with deficiency of N-glycanase 1.

Methods: Whole-genome, whole-exome, or standard Sanger sequencing techniques were employed.