title: Molecular diagnosis of infantile Neuro axonal Dystrophy by Next Generation Sequencing.
abstract: Infantile Neuro axonal Dystrophy (INAD), is a rare inherited neurological disorder which affects nerve axons causing progressive loss of mental skills, muscular control and vision. The authors present a case of 5.8-y-old girl with INAD who was diagnosed after Next Generation Sequencing (NGS). She was born to a non-consanguineous couple and presented with hypotonia, developmental delay followed by neuroregression and nystagmus after 2 years of age. On examination, bilateral horizontal nystagmus and normal head circumference were noted. Brain MRI showed cerebellar atrophy and altered signal intensities in bilateral globus pallidi and thalami. Magnetic resonance spectroscopy (MRS) showed elevation of lactate. Metabolic testing with Tandem Mass Spectrometry (TMS) and Gas Chromatography Mass Spectrometry (GC-MS) were normal. Mitochondrial disorder was suspected in view of clinical presentation, increased lactate and neuro-imaging suggestive of Leigh syndrome. Mitochondrial Leigh mutations and SURF1 gene sequencing yielded normal results. Lack of a clear diagnosis led to performance of NGS using panel of about 514 genes. A homozygous novel mutation at position c.2277-1G>C in PLA2G6 gene presumed to give rise to altered splicing, was detected, thus confirming the diagnosis of INAD. This report provides evidence of the usefulness of NGS technology as a quick and accurate diagnostic tool for an otherwise complicated genetic disease. To the authors knowledge, this is the first case report with mutations in PLA2G6 gene from India.
authors.affiliation: Division of Genetics & Metabolism, Department of Pediatrics, Maulana Azad Medical College, New Delhi, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Goyal
authors.forename: Sunita
authors.initials: S
authors.lastname: Bijarnia-Mahay
authors.forename: Stephen
authors.initials: S
authors.lastname: Kingsmore
authors.forename: Emily
authors.initials: E
authors.lastname: Farrow
authors.forename: Carol
authors.initials: C
authors.lastname: Saunders
authors.forename: Renu
authors.initials: R
authors.lastname: Saxena
authors.forename: Ishwar C
authors.initials: IC
authors.lastname: Verma
mesh_terms: D002675:Child, Preschool; D005260:Female; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009154:Mutation; D019150:Neuroaxonal Dystrophies / Q000175:diagnosis / Q000235:genetics*; D053719:Tandem Mass Spectrometry
chemical_list: D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human