TY - JOUR
T1 - The prevalence of diseases caused by lysosome-related genes in a cohort of undiagnosed patients
AU - Vairo, Filippo Pinto
AU - Boczek, Nicole J.
AU - Cousin, Margot A.
AU - Kaiwar, Charu
AU - Blackburn, Patrick R.
AU - Conboy, Erin
AU - Lanpher, Brendan C.
AU - Gavrilova, Ralitza H.
AU - Pichurin, Pavel N.
AU - Lazaridis, Konstantinos N.
AU - Babovic-Vuksanovic, Dusica
AU - Klee, Eric W.
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/12
Y1 - 2017/12
N2 - Lysosomal diseases (LD) comprise a group of approximately 60 hereditary conditions caused by progressive accumulation of metabolites due to defects in lysosomal enzymes and degradation pathways, which lead to a wide range of clinical manifestations. The estimated combined incidence of LD is between 1 in 4000 to 1 in 13,000 live births, with recent data from pilot newborn screening studies showing even higher incidence. We aimed to determine the prevalence of the classical LD and other diseases caused by lysosome-related genes in our cohort of diagnostic odyssey patients. The Individualized Medicine Clinic at Mayo Clinic is increasingly utilizing whole exome sequencing (WES) to determine the genetic etiology of undiagnosed Mendelian disease. From September 2012 to April 2017, WES results from 350 patients with unexplained symptoms were reviewed. Disease-causing variants were identified in MYO6, CLN6, LRBA, KCTD7, and ARSB revealing a genetic diagnosis of a LD in 8 individuals from 5 families. Based on our findings, lysosome-related disorders may be collectively common, reaching up to 1.5% prevalence in a cohort of patients with undiagnosed diseases presenting to a genetics clinic.
AB - Lysosomal diseases (LD) comprise a group of approximately 60 hereditary conditions caused by progressive accumulation of metabolites due to defects in lysosomal enzymes and degradation pathways, which lead to a wide range of clinical manifestations. The estimated combined incidence of LD is between 1 in 4000 to 1 in 13,000 live births, with recent data from pilot newborn screening studies showing even higher incidence. We aimed to determine the prevalence of the classical LD and other diseases caused by lysosome-related genes in our cohort of diagnostic odyssey patients. The Individualized Medicine Clinic at Mayo Clinic is increasingly utilizing whole exome sequencing (WES) to determine the genetic etiology of undiagnosed Mendelian disease. From September 2012 to April 2017, WES results from 350 patients with unexplained symptoms were reviewed. Disease-causing variants were identified in MYO6, CLN6, LRBA, KCTD7, and ARSB revealing a genetic diagnosis of a LD in 8 individuals from 5 families. Based on our findings, lysosome-related disorders may be collectively common, reaching up to 1.5% prevalence in a cohort of patients with undiagnosed diseases presenting to a genetics clinic.
KW - Inborn errors of metabolism
KW - Lysosomal disorders
KW - Lysosomal storage disorders
KW - Rare diseases
KW - Undiagnosed diseases
KW - Whole exome sequencing
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U2 - 10.1016/j.ymgmr.2017.08.001
DO - 10.1016/j.ymgmr.2017.08.001
M3 - Article
AN - SCOPUS:85027686874
SN - 2214-4269
VL - 13
SP - 46
EP - 51
JO - Molecular Genetics and Metabolism Reports
JF - Molecular Genetics and Metabolism Reports
ER -