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Sibling illness may contribute to an increased risk of adjustment problems in healthy siblings. Previous studies have reported a variety of effects on healthy individuals who have an ill sibling, but the psychosocial effects of treatable inherited disease on healthy siblings have not yet been investigated. We report the results of a survey study conducted in families with both unaffected and affected children with classic phenylketonuria (PKU), an inherited inborn error of metabolism. The survey included a knowledge test about PKU, and four previously validated instruments designed to assess psychosocial adjustment of unaffected siblings compared to age and sex matched norms. The responses revealed that unaffected adolescent and adult siblings had gaps in their knowledge about the genetic basis of PKU, and had evidence for the presence of adverse psychosocial sequelae. These findings suggest a role for genetic services providers, including genetic counselors, in assisting all members of a family adjust, when the diagnosis of an inborn error of metabolism has been made.

We report the results of linkage analysis in a large American family of Czech descent with dominantly inherited "Pure" essential tremor (ET) and genetic anticipation. Genetic loci on chromosome 2p22‐p25 establish linkage to this region with a maximum LOD score (Zmax) = 5.92 for the locus, D2S272. Obligate recombinant events place the ETM gene in a 15‐cM candidate interval between the genetic loci D2S168 and D2S224. Repeat expansion detection analysis suggests that expanded CAG trinucleotide sequences are associated with ET. These findings will facilitate the search for an ETM gene and may further our understanding of the human motor system.

The autosomal dominant ataxias (ADA) are a diverse group of multisystem, neurodegenerative disorders characterized by mutations at several chromosomal loci (SCA types 1–5, SCA type 7, DRPLA). We excluded all the known SCA loci by mutational and linkage analyses in an American family of British origin with ADA and document that an additional ataxia locus must exist. The clinical characteristics and ethnic origin of our family are similiar to the British Drew family of Walworth with the SCA type 3 mutation and differ from other families without a known ataxia locus. Individuals in our family and the Drew family initially show signs of ataxia but may develop variable degrees of ophthalmoplegia, Parkinsonian features and central demyelination. The phenotypic diversity in families without a known ataxia locus suggests that there may be several other undefined ataxia loci.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmed significant familial aggregation of PD and a large number of large multicase families have been documented. Genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380. This finding will facilitate identification of the gene and research on the pathogenesis of PD.

Development of DNA-mediated transfection in Entamoeba histolytica will facilitate basic research toward the control of this protozoan parasite. A transient transfection system was established by using the firefly luciferase gene ligated to the 5' and 3' flanking regions of the amebic hgl1 gene. The optimal construct tested encoded an hgl1-luciferase fusion protein and contained 1 kb of 5' flanking sequence with 16 bases of coding sequence from the hgl1 gene ligated in-frame to the luciferase start codon and 2.3 kb of 3' flanking sequence from hgl1 ligated 3' to the luciferase stop codon. Optimal electroporation conditions in strain HM-1:IMSS trophozoites when using this construct were 500 microF and 500 V/cm, which resulted in luciferase activity up to 5000-fold above background 9-12 hr after electroporation. Constructs that contained the luciferase gene without amebic flanking sequences or that contained a simian virus 40 promoter, enhancer, and polyadenylylation signal produced only background levels of luciferase activity. The ability to introduce and express genes in amebae will now permit a genetic analysis of the virulence of this organism, which remains a serious threat to world health.