Dosage effects of cohesin regulatory factor PDS5 on mammalian development: implications for cohesinopathies.

Cornelia de Lange syndrome (CdLS), a disorder caused by mutations in cohesion proteins, is characterized by multisystem developmental abnormalities. PDS5, a cohesion protein, is important for proper chromosome segregation in lower organisms and has two homologues in vertebrates (PDS5A and PDS5B). Pds5B mutant mice have developmental abnormalities resembling CdLS; however the role of Pds5A in mammals and the association of PDS5 proteins with CdLS are unknown.

Human 3beta-hydroxysteroid dehydrogenase types 1 and 2: Gene sequence variation and functional genomics.

The 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase isoenzymes 1 and 2 (HSD3B1 and HSD3B2) are membrane-bound enzymes that play essential roles in the biosynthesis of steroid hormones. Therefore, variation in the HSD3B1 and HSD3B2 genes might play a role in the pathophysiology of steroid hormone-related disease. We set out to systematically identify common polymorphisms and haplotypes in human HSD3B1 and HSD3B2.

Familial parkinsonism and ophthalmoplegia from a mutation in the mitochondrial DNA helicase twinkle.

Objective: To describe the clinical phenotype and genetic basis of a family with autosomal dominant progressive external ophthalmoplegia and parkinsonism from a Twinkle mutation.

Design: All coding exons of POLG1, Twinkle (aka C10ORF2, PEO1), and ANT1 (SLC25A4) were sequenced in the proband with targeted sequencing of the Twinkle gene in all additional subjects.

Subjects: Members of a 3-generation family followed up in a neuromuscular disease center for dominantly inherited progressive external ophthalmoplegia.