Tuberous sclerosis is a dominantly inherited genetic disorder, with a high frequency of new mutations, which has been shown through genetic linkage studies to be genetically heterogeneous. In this paper we summarize recent progress in linkage studies which indicate that there is one TSC gene on chromosome 9q34 which accounts for approximately 40% of cases and another on chromosome 16p13.3 which accounts for approximately 50% of cases. We discuss the map position of these TSC genes on chromosome 9q34 and 16p13.3. We discuss physical mapping data in these two regions. We postulate on the pathogenesis of TSC lesions and on the cause of the high frequency of new mutations. We present a strategy to progress from the mapping of the TSC genes to isolation of these genes.

The breadth and scope of new information makes difficult a selection of topics to be included in a limited review of highlights of the year. Admittedly, the choices are idiosyncratic. The eight topics presented here are (1) structural and copy number variants in the human genome; (2) progress in defining genetic factors in the etiology of schizophrenia; (3) microRNAs in central nervous system development and function; (4) progress in elucidation of risk factors for complex common disorders through large scale association studies; (5) epigenetics and the epigenomic era; (6) reprogramming of somatic cell nuclei to generate pluripotent stem cells; (7) new concepts regarding factors involved in sexual differentiation; and (8) Duffy blood group antigens: new concepts, and new discoveries on the role of these antigens in malaria and HIV-AIDS.

The 3 conditions that should be considered in the differential diagnosis of individual ls of predominantly female phenotype who prove to be chromatin negative and 10 have an XY karyotype a re male pseudohermaphrodilism. testicular feminization and gonadal dysgenesis. The clinical finding in the patient reported here suggested the diagnosis of gonadal dysgenesis and this diagnosis was subsequently confirmed by gonadal histology.