Identification of an HMGB3 frameshift mutation in a family with an X-linked colobomatous microphthalmia syndrome using whole-genome and X-exome sequencing.

Importance: Microphthalmias are rare disorders whose genetic bases are not fully understood. HMGB3 is a new candidate gene for X-linked forms of this disease.

Objective: To identify the causative gene in a pedigree with an X-linked colobomatous microphthalmos phenotype.

Inherited surfactant deficiency caused by uniparental disomy of rare mutations in the surfactant protein-B and ATP binding cassette, subfamily a, member 3 genes.

Objective: To characterize inheritance of homozygous, rare, recessive loss-of-function mutations in surfactant protein-B (SFTPB) or ATP binding cassette, subfamily A, member 3 (ABCA3) genes in newborns with lethal respiratory failure.

Study Design: We resequenced genes from parents whose infants were homozygous for mutations in SFTPB or ABCA3. For infants with only 1 heterozygous parent, we performed microsatellite analysis for chromosomes 2 (SFTPB) and 16 (ABCA3).

Hypoxia-inducible factor 1alpha polymorphism and coronary collaterals in patients with ischemic heart disease.

Study Objectives: Marked variability exists in coronary artery collaterals in patients with ischemic heart disease. Although multiple factors are thought to play a role in collateral development, the contribution of genetic factors is largely unknown. Hypoxia inducible factor 1 (HIF-1), a transcriptional activator that functions as a master regulator of oxygen homeostasis, is one possible genetic factor that could play an important role in modulating collateral development.

Genetic and environmental risk factors for sagittal craniosynostosis.

The authors investigated whether genetic and environmental factors influence risk for sagittal craniosynostosis. Cases were ascertained from craniofacial clinics in the Baltimore-Washington metropolitan region. Controls were recruited from the Johns Hopkins newborn nursery and a large pediatric practice in Baltimore County.

Strategies for genotyping: Effectiveness of tailing primers to increase accuracy in short tandem repeat determinations.

A problem associated with automated analysis of fluorescently labeled fragments separated by slab gel or capillary electrophoresis is the doublet peak formed when Taq DNA Polymerase adds a nontemplated nucleotide (generally an adenosine) to the 3' end of the product.This nontemplated addition (plus A) is primarily dependent on the 5' sequence of the reverse primer and, to a lesser extent, polymerase chain reaction (PCR) conditions. Primers may amplify the true product, the plus A product or a doublet product comprised of both.