Open AccessDiagnosis of D-Bifunctional Protein Deficiency through Whole-Genome Sequencing: Implications for Cost-Effective Care
Author(s) -
Alina Khromykh,
Benjamin D. Solomon,
Dale L. Bodian,
Eyby Leon,
Ramaswamy K. Iyer,
Robin Baker,
David P. Ascher,
Rajiv Baveja,
Joseph G. Vockley,
John E. Niederhuber
Publication year - 2015
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000433621
Subject(s) - newborn screening , whole genome sequencing , medicine , mutation , dna sequencing , bioinformatics , occult , genetic testing , omics , computational biology , genome , genetics , gene , biology , pediatrics , pathology , alternative medicine
D-Bifunctional protein deficiency, caused by recessive mutations in HSD17B4, is a severe disorder of peroxisomal fatty acid oxidation. Nonspecific clinical features may contribute to diagnostic challenges. We describe a newborn female with infantile-onset seizures and nonspecific mild dysmorphisms who underwent extensive genetic workup that resulted in the detection of a novel homozygous mutation (c.302+1_4delGTGA) in the HSD17B4 gene, consistent with a diagnosis of D-bifunctional protein deficiency. By comparing the standard clinical workup to diagnostic analysis performed through research-based whole-genome sequencing (WGS), which independently identified the causative mutation, we demonstrated the ability of genomic sequencing to serve as a timely and cost-effective diagnostic tool for the molecular diagnosis of apparent and occult newborn diseases. As genomic sequencing becomes more available and affordable, we anticipate that WGS and related omics technologies will eventually replace the traditional tiered approach to newborn diagnostic workup.