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BackgroundStudies indicate that variants of uncertain significance are more common in non-European populations due to lack of a diversity in population databases. This difference has not been explored in epilepsy, which is increasingly found to be genetic in paediatric populations, and has precision medicine applications. This study examines the differences in the frequency of uncertain next-generation sequencing (NGS) results among a paediatric epilepsy cohort between ancestral groups historically under-represented in biomedical research (UBR) and represented in biomedical research (RBR).MethodsA retrospective chart review of patients with epilepsy seen at Columbia University Irving Medical Center (CUIMC). One hundred seventy-eight cases met the following criteria: (1) visited any provider within the Pediatric Neurology Clinic at CUIMC, (2) had an ICD code indicating a diagnosis of epilepsy, (3) underwent NGS testing after March 2015 and (4) had self-reported ancestry that fit into a single dichotomous category of either historically represented or under-represented in biomedical research.ResultsUBR cases had significantly higher rates of uncertain results when compared with RBR cases (79.2% UBR, 20.8% RBR; p value=0.002). This finding remained true after controlling for potential confounding factors, including sex, intellectual disability or developmental delay, epilepsy type, age of onset, number of genes tested and year of testing.ConclusionOur results add to the literature that individuals who are of ancestries historically under-represented in genetics research are more likely to receive uncertain genetic results than those of represented majority ancestral groups and establishes this finding in an epilepsy cohort.

By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS).

Epilepsy is a highly complex disease and is one of the most common neurological conditions worldwide. Some 2,500 years after Hippocrates observed a hereditary tendency for epilepsy, researchers discovered the [...]

Although consensus is building that primary (PR) and secondary findings (SF) from genomic research should be offered to participants under some circumstances, data describing (1) actual choices of study participants and (2) factors associated with these choices are limited, hampering study planning. We conducted a cross-sectional analysis of choices made for return of PR and SF during informed consent by members of the first 247 families (790 individuals) enrolled in the Baylor-Hopkins Center for Mendelian Genomics, a genome sequencing study. Most (619; 78.3%) chose to receive SF and PR, 66 (8.4%) chose PR only, 65 (8.2%) wanted no results, and 40 (5.1%) chose SF only. Choosing SF was associated with an established clinical diagnosis in the proband (87.8 vs 79%, P=0.009) and European ancestry (EA) (87.7 vs 73%, P<0.008). Participants of non-European ancestry (NEA) were as likely as those of EA to choose SF when consented by a genetic counselor (GC) (82% NEA vs 88.3% EA, P=0.09) but significantly less likely when consented by a physician (67.4% NEA vs 85.4% EA, P=0.001). Controlling for proband diagnosis, individuals of NEA were 2.13-fold (95% CI: 1.11–4.08) more likely to choose SF when consented by a GC rather than a physician. Participants of NEA were 3-fold more likely than those of EA to decline all study results (14.7% NEA vs 5.4% EA, P<0.008). In this ethnically diverse population, whereas most participants desired PR and SF, more than 20% declined some or all results, highlighting the importance of research participant choice.

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Peters Plus syndrome comprises ocular anterior segment dysgenesis most commonly Peters anomaly, short stature, hand anomalies, distinctive facial features, and often other additional defects and is inherited in an autosomalrecessive pattern. Mutations in the β1,3glucosyltransferase gene B3GALTL were recently reported in 20 out of 20 patients with Peters Plus syndrome. In our study, B3GALTLwas examined in four patients with typical Peters Plus syndrome and four patients that demonstrated a phenotypic overlap with this condition. Mutations in B3GALTLwere identified in all four patients with typical Peters Plus syndrome, while no mutations were found in the remaining four patients that demonstrated some but not all characteristic features of the syndrome. The previously reported common mutation, c.660  1G > A, accounted for 75 of the mutant alleles in our Peters Plus syndrome population. In addition, two new mutant alleles, c.459  1G > A and c.230insT, were identified and predicted to result in truncated protein products. These data confirm an important role for B3GALTLin causing typical Peters Plus syndrome, and suggest that this gene may not be implicated in syndromic cases that involve Peters anomaly but lack other classic features of this complex condition. © 2008 WileyLiss, Inc.

Schwannomatosis is a neurogenetic syndrome characterized by schwannomas throughout the peripheral nervous system without bilateral vestibular schwannomas (VS) or germline neurofibromatosis 2 (NF2) mutation.1Management is difficult due to large tumor burden and treatment-resistant pain. Patients require multiple surgical procedures (average of 3.4 per decade) for pain, focal neurologic deficits, or myelopathy.1There are no known effective drug therapies.