Novel mutations in XLRS1 causing retinoschisis, including first evidence of putative leader sequence change

Juvenile retinoschisis is an X-linked recessive disease caused by mutations in the XLRS1 gene. We screened 31 new unrelated patients and families for XLRS1 mutations in addition to previously reported mutations for 60 of our families (Retinoschisis Consortium, Hum Mol Genet 1998;7:1185–1192). Twenty-three different mutations including 12 novel ones were identified in 28 patients. Mutations identified in this study include 19 missense mutations, two nonsense mutations, one intragenic deletion, four microdeletions, one insertion, and one intronic sequence substitution that is likely to result in a splice site defect. Two novel mutations, c.38T→C (L13P) and c.667T→C (C223R), respectively, present the first genetic evidence for the functional significance of the putative leader peptide sequence and for the functional significance at the carboxyl terminal of the XLRS1 protein beyond the discoidin domain. Mutations in 25 of the families were localized to exons 4–6, emphasizing the critical functional significance of the discoidin domain of the XLRS1 protein. Hum Mutat 14:423–427, 1999. © 1999 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35178/1/8_ftp.pd

Robert Edwards: the path to IVF☆

The early influences on Robert Edwards’ approach to the scientific research that led to human IVF are described. His interest as a graduate student in the genetics of early mammalian development stimulated him later to investigate whether the origins of human genetic diseases such as Down, Klinefelter and Turner syndromes might be explained by events during egg maturation. This clinical problem provided the most powerful stimulus to achieve both oocyte maturation and fertilization in vitro in humans. Indeed, preimplantation genetic diagnosis was his main goal until he met Patrick Steptoe in 1968. A re-evaluation of his meeting with Steptoe suggests that initially Steptoe’s laparoscopic skill was of interest for its potential to solve the sperm capacitation problem. Steptoe’s impact on Edwards was twofold. First, Steptoe’s long-held interest in infertility raised this application of IVF higher in Edwards’ priorities. Second, Steptoe offered a long-term partnership, in which oocyte collection without in-vitro maturation was a possibility. The professional criticism generated by their work together encouraged Edwards to pursue a deliberate programme of public education about the issues raised and to challenge and develop professional bioethical thought and discourse about reproduction