The scientific process of analysis and deduction is frequently, often subconsciously, used by physicians to develop a differential diagnosis based on patients' symptoms. Common disorders are most frequently diagnosed in general practice. Rare diseases are uncommon and frequently remain undiagnosed for many years. Cognitive errors in clinical judgment delay definitive diagnosis. Whole-exome sequ...

Autosomal recessive cerebellar ataxia encompasses a large and heterogeneous group of neurodegenerative disorders. We employed single nucleotide polymorphism (SNP) analysis and whole exome sequencing to investigate a consanguineous Maori pedigree segregating ataxia. We identified a novel mutation in exon 10 of the SACS gene: c.7962T>G p.(Tyr2654*), establishing the diagnosis of autosomal recessi...

An association of congenital diaphragmatic hernia, dandy walker malformation and nasopharyngeal teratoma is very rare. Here, we report a fourth case with this association where chromosomal microarray and whole exome sequencing (WES) was performed to understand the underlying genetic basis. Findings of few variants especially a novel variation in HIRA provided some insights. An association of co...

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvi CHAPTER 1. GENERAL INTRODUCTION . . . . . . . . . . . . . . . . . . . 1 1.1 HLA typing and related applications . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1.1 HLA genes and their function . . . . . . . . . . . . . . . . . . . . . . . . 2 1.1.2 HLA diversity and nomenclature . . . . . . . . . . . . . . . ....

Genotyping chips for rare and low-frequent variants have recently gained popularity with the introduction of exome chips, but the utility of these chips remains unclear. These chips were designed using exome sequencing data from mainly American-European individuals, enriched for a narrow set of common diseases. In addition, it is well-known that the statistical power of detecting associations w...

This editorial examines a number of vitally important ethical, legal and scientific concerns that have to be addressed to ensure proper and ethical implementation of direct-to-consumer whole-exome sequencing in South Africa. Individuals taking part in this endeavour must be fully informed of the positive and negative sequelae.

OBJECTIVE To develop a comprehensive and efficient assessment tool for rheumatic condition-related work barriers and explore its use by physical and occupational therapists. METHODS Literature on arthritis work barriers was examined, followed by the collection of qualitative data on work barriers from patients with rheumatic conditions. A tool called the Work Experience Survey-Rheumatic Condi...

High-throughput sequencing technologies have allowed for the cataloguing of variation in personal human genomes. In this manuscript, we present alu-detect, a tool that combines read-pair and split-read information to detect novel Alus and their precise breakpoints directly from either whole-genome or whole-exome sequencing data while also identifying insertions directly in the vicinity of exist...

We present a sibling pair with Leigh-like disease, progressive hypotonia, regression, and chronic encephalopathy. Whole exome sequencing in the younger sibling demonstrated a homozygous thiamine pyrophosphokinase (TPK) mutation. Initiation of high dose thiamine, niacin, biotin, α-lipoic acid and ketogenic diet in this child demonstrated improvement in neurologic function and re-attainment of pr...

OBJECTIVE To determine the genetic basis of an unexplained multisystem neurological disorder affecting 2 siblings. DESIGN Case reports and whole-exome DNA sequencing. SETTING Neurogenetics clinic, Institute of Genetic Medicine, Newcastle upon Tyne, England. PATIENTS Two adult siblings with a sensorimotor neuropathy, ataxia, and spasticity. MAIN OUTCOME MEASURES Clinical, neurophysiologi...