UNASSIGNED: @entity1687 ( @entity1687 ) is a rare @entity14827 featuring pleiotropic neurological, @entity146 and visceral manifestations. Since many of the adult manifestations can be non-specific or missed, @entity1687 often goes undetected in adult-onset @entity1 . Here we hypothesized that targeted high-throughput sequencing allows identifying @entity1687 @entity1 among subjects with unexplained early-onset @entity2055 (EOA) and, moreover, that this population is enriched for @entity38153 mutations. From 204 consecutive EOA @entity1 , all 108 subjects with an established diagnosis were removed (including 4 @entity38153 @entity1 ), yielding a target cohort of 96 subjects with unexplained EOA, but without primary suspicion of @entity1687 . This cohort was investigated for @entity38153 / @entity59317 mutations using a high-coverage HaloPlex gene panel including 122 @entity2055 genes. Among 96 samples, we identified 4 known @entity38153 mutations, 3 novel @entity38153 missense variants of uncertain significance (VUS) and 1 novel @entity59317 missense VUS. The total mutant allele frequency (8/192  =  4.17  %) was significantly enriched compared with control population data (1.57  %; p  =  0.011). Two @entity38153 -positive @entity1 were identified (both with non-specific incipient clinical features), giving a @entity38153 @entity1 frequency of 2/96  =  2.1  % in unexplained EOA and of 6/204  =  2.9  % in the total EOA series. @entity38153 mutations are substantially enriched in unexplained EOA, demonstrating EOA as a risk-group for @entity1687 disease. Targeted high-throughput sequencing allows to identify also those @entity1687 @entity1 with non-specific conditions where the diagnosis has initially been missed. This method does not require having considered @entity1687 during differential diagnosis, but allows identification of @entity1687 as part of the default analysis.

XXXX is enriched in unexplained early onset @entity2055 : a targeted high-throughput screening.

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity59317 :: ('10577', 'Gene') :: ['NPC2'] @entity146 :: ('MESH:D001523', 'Disease') :: ['psychiatric'] @entity38153 :: ('4864', 'Gene') :: ['NPC1'] @entity1687 :: ('MESH:D052556', 'Disease') :: ['NP-C', 'Niemann-Pick disease type C'] @entity14827 :: ('MESH:D020271', 'Disease') :: ['autosomal-recessive neurodegenerative disease'] @entity2055 :: ('MESH:D001259', 'Disease') :: ['ataxia']
@entity38153 :: (4864,Gene) :: ['NPC1']
