Background Arterial calcifications are associated with increased cardiovascular risk, but the
genetic basis of this association is unclear. Methods We performed clinical, radiographic, …

Background The lysosomal storage disease cystinosis results in renal failure at approximately
10 years of age. Although oral cysteamine therapy is recognized to preserve kidney …

Purpose: This report describes the National Institutes of Health Undiagnosed Diseases
Program, details the Program’s application of genomic technology to establish diagnoses, and …

Objective Early‐onset epileptic encephalopathies have been associated with de novo
mutations of numerous ion channel genes. We employed techniques of modern translational …

Background Mutations in the FBN1 gene are the cause of the Marfan syndrome, an autosomal
dominant disorder with skeletal, ocular, and cardiovascular complications. Aneurysms or …

We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous
family characterized clinically by lower extremity spasticity, peripheral neuropathy, …

Disease gene discovery has been transformed by affordable sequencing of exomes and
genomes. Identification of disease‐causing mutations requires sifting through a large number of …

One major challenge encountered with interpreting human genetic variants is the limited
understanding of the functional impact of genetic alterations on biological processes. …

Diagnosis at the edges of our knowledge calls upon clinicians to be data driven, cross-disciplinary,
and collaborative in unprecedented ways. Exact disease recognition, an element of …

Introduction The inability of some seriously and chronically ill individuals to receive a definitive
diagnosis represents an unmet medical need. In 2008, the NIH Undiagnosed Diseases …