PURPOSE With advances in phenotyping tools and availability of molecular characterization, an increasing number of phenotypically and genotypically diverse inherited corneal dystrophies are described. We aimed to determine the underlying causative genetic mechanism in a three-generation pedigree affected with a unique anterior membrane corneal dystrophy characterized by early onset recurrent co...

BACKGROUND Targeted postmortem genetic testing of the 4 major channelopathy-susceptibility genes (KCNQ1, KCNH2, SCN5A, and RYR2) have yielded putative pathogenic mutations in ≤30% of autopsy-negative sudden unexplained death in the young (SUDY) cases with highest yields derived from the subset of exertion-related SUDY. Here, we evaluate the role of whole-exome sequencing in exertion-related SUD...

Leucine-rich repeat kinase 2 (LRRK2) gene mutations are the most common genetic cause of Parkinson's disease (PD). More than 300 rare LRRK2 variants have been described, with approximately 17 having confirmed or probable pathogenic role in PD. The distribution differs across ethnic groups, but no PD-related variant has described persons Black African ancestry within outside Africa. We previousl...

PURPOSE To describe the complex, overlapping phenotype expressed in a two generation family harboring pathogenic mutations in the ABCA4 and GPR143 genes. METHODS Clinical evaluation of a two generation family included quantitative autofluorescence imaging (qAF, 488-nm excitation) using a modified confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account...

Next generation sequencing is extensively applied to catalogue somatic mutations in cancer, in research settings and increasingly in clinical settings for molecular diagnostics, guiding therapy decisions. Somatic variant callers perform paired comparisons of sequencing data from cancer tissue and matched normal tissue in order to detect somatic mutations. The advent of many new somatic variant ...

Case presentation: Girl, 5 years old, she had not gestational and neonatal complications her parents is consanguineous. She neuropsychomotor developmental delay (NDD) dysphagia for solids at 6 months. At 2 cognitive impairment, motor with axial ataxia, appendicular hypotonia dysmetria. Her symptoms progressively worsening associated pyramidal signs. Cerebellar atrophy increased arachnoid space ...

Sequence variants of human mitochondrial DNA (mt DNA) have been implicated in a variety disorders and conditions. Massive parallel sequencing is becoming increasingly popular due to its efficiency cost-effectiveness. In relation acquiring significant sequence information like levels heteroplasmy mt DNA, it offers marked improvement compared previous methods used. Here we describe variant callin...

Causative germline mutations in mismatch repair (MMR) genes can only be identified in ~50% of families with a clinical diagnosis of the inherited colorectal cancer (CRC) syndrome hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome (LS). Identification of these patients are critical as they are at substantially increased risk of developing multiple primary tumors, mainly colorectal ...