GNAS1 mutation and Cbfa1 misexpression in a child with severe congenital platelike osteoma cutis.

We evaluated a 7-year-old girl with severe platelike osteoma cutis (POC), a variant of progressive osseous heteroplasia (POH). The child had congenital heterotopic ossification of dermis and subcutaneous fat that progressed to involve deep skeletal muscles of the face, scalp, and eyes. Although involvement of skeletal muscle is a prominent feature of POH, heterotopic ossification has not been observed in the head, face, or extraocular muscles. The cutaneous ossification in this patient was suggestive of Albright hereditary osteodystrophy (AHO); however, none of the other characteristic features of AHO were expressed. Inactivating mutations of the GNAS1 gene, which encodes the alpha-subunit of the stimulatory G protein of adenylyl cyclase, is the cause of AHO. Mutational analysis of GNAS1 using genomic DNA of peripheral blood and of lesional and nonlesional tissue from our patient revealed a heterozygous 4-base pair (bp) deletion in exon 7, identical to mutations that have been found in some AHO patients. This 4-bp deletion in GNAS1 predicts a protein reading frameshift leading to 13 incorrect amino acids followed by a premature stop codon. To investigate pathways of osteogenesis by which GNAS1 may mediate its effects, we examined the expression of the obligate osteogenic transcription factor Cbfa1/RUNX2 in lesional and uninvolved dermal fibroblasts from our patient and discovered expression of bone-specific Cbfa1 messenger RNA (mRNA) in both cell types. These findings document severe heterotopic ossification in the absence of AHO features caused by an inactivating GNAS1 mutation and establish the GNAS1 gene as the leading candidate gene for POH.

Abortion policy and politics on the Lane Committee of Enquiry, 1971-1974.

The 1967 Abortion Act did not quell public discussion on therapeutic abortions in Britain. Criticism of the way the Act was working began almost as soon as the legislation came into force. After only three years, a committee of enquiry, chaired by Justice Elizabeth Lane, studied the working of the Act. This Committee caused some surprise on all sides of the abortion debate by offering unanimous support for the Act in its original form. Understanding how the Lane Committee arrived at its unexpected recommendations is important not only because the Report has proved to be an enduring endorsement of the Act but also because the Lane Committee provides a case study of the process of policy formulation at the level of a committee of enquiry. The Lane Committee appears to have achieved consensus incrementally. First a majority and then the whole Committee supported the Act as a humane measure requiring regulatory and not legislative solutions to the problems of its working. Using both written and oral sources, I will argue that consensus evolved through the compelling leadership of several key members of the majority group with particular influence by the most psychosocially oriented members of the Committee.