Exome sequencing as a diagnostic tool in a case of undiagnosed juvenile-onset GM1-gangliosidosis.

[gm1 gangliosidosis]

To utilize high -throughput sequencing to determine the etiology of juvenile -onset neurodegeneration in a 19 -year -old woman with progressive motor and cognitive decline .Exome sequencing identified an initial list of 133 ,555 variants in the proband 's family , which were filtered using segregation analysis , presence in dbSNP , and an empirically derived gene exclusion list . The filtered list comprised 52 genes : 21 homozygous variants and 31 compound heterozygous variants . These variants were subsequently scrutinized with predicted pathogenicity programs and for association with appropriate clinical syndromes .Exome sequencing data identified 2 GLB 1 variants (c .602 G >A , p .R 201 H ; c .785 G >T , p .G 262 V ). Î²-Galactosidase enzyme analysis prior to our evaluation was reported as normal ; however , subsequent testing was consistent with juvenile -onset GM 1 -gangliosidosis . Urine oligosaccharide analysis was positive for multiple oligosaccharides with terminal galactose residues .We describe a patient with juvenile -onset neurodegeneration that had eluded diagnosis for over a decade . GM 1 -gangliosidosis had previously been excluded from consideration , but was subsequently identified as the correct diagnosis using exome sequencing . Exome sequencing can evaluate genes not previously associated with neurodegeneration , as well as most known neurodegeneration -associated genes . Our results demonstrate the utility of "agnostic " exome sequencing to evaluate patients with undiagnosed disorders , without prejudice from prior testing results .

Diseases
Validation

Diseases presenting "neurodegeneration" symptom

adrenomyeloneuropathy

alexander disease

cadasil

canavan disease

classical phenylketonuria

fabry disease

gm1 gangliosidosis

hereditary cerebral hemorrhage with amyloidosis

krabbe disease

neonatal adrenoleukodystrophy

neuralgic amyotrophy

oculocutaneous albinism

pyruvate dehydrogenase deficiency

triple a syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

This symptom has already been validated