One DFNB12 allele in trans configuration to an USH1D allele of CDH23 preserves vision and balance in deaf individuals, indicating that the DFNB12 allele is phenotypically dominant to an USH1D allele. This finding has implications for genetic counselling and the development of therapies for retinitis pigmentosa in Usher syndrome. ACCESSION NUMBERS: The cDNA and protein Genbank accession numbers for CDH23 and cadherin 23 used in this paper are AY010111.2 and AAG27034.2, respectively.

BACKGROUND:The global lapatinib expanded access programme provided access to lapatinib combined with capecitabine for women with HER2-positive metastatic breast cancer (MBC) who previously received anthracycline, taxane and trastuzumab. METHODS: Progression-free survival (PFS) and safety data for 356 patients recruited from the United Kingdom are reported. Efficacy was assessed in 162 patients from the five lead centres, including objective tumour response rate (ORR), time to disease progression (TTP) and efficacy in those with central nervous system (CNS) metastases. Correlation of PFS and ORR with previous capecitabine treatment was also documented. RESULTS: Overall, PFS for the 356 UK patients was 21 weeks (95% CI: 17.6 -24.7). In the 162 assessable patients, ORR was 21% (95% CI: 15 -27%) and median TTP was 22 weeks (95% CI: 17 -27). Efficacy was greater in capecitabine-naive patients (ORR 23 vs 16.3%, P ¼ 0.008). For 34 patients with CNS metastases, ORR was 21% (95% CI: 9 -39%), with evidence of improvement in neurological symptoms, and median TTP was 22 weeks (95% CI: 15 -28). CONCLUSIONS: Lapatinib combined with capecitabine is an active treatment option for women with refractory HER2-positive MBC, including those with progressive CNS disease.

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Prostate specific antigen levels were measured in 118 patients with prostatic cancer and 138 control individuals. Prostate specific antigen was sensitive in detecting prostatic cancer. The levels of prostate specific antigen were elevated in 10 per cent of the patients with stage A, 24 per cent with stage B, 53 per cent with stage C and 92 per cent with stage D disease. However, prostate specific antigen levels also were elevated in 9 per cent of the patients with benign prostatic hypertrophy. This lack of specificity in the presence of benign prostatic hypertrophy probably precludes prostate specific antigen from being recommended as a screening test for prostatic cancer. The ultimate role of prostate specific antigen might be as the marker of choice to monitor therapy for prostatic carcinoma.

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Consanguinity has highly complex and multifaceted aspects with sociocultural as well as biological debates on its pros and cons. The biological upshot of consanguinity includes the increased homozygosity, which results in manifold increased risk of genetic disorders at family and population levels. On the other hand, in addition to social, cultural, political, and economic benefits, consanguineous marriages have biological advantages at the population level. The consequence of consanguineous marriages is an upsurge in the number of homozygous diseased individuals with fewer chances of mating and reduced chances of survival, therefore evolutionarily confining the transmission of disease alleles to future generations and encouraging its elimination from a population. Protective effects of consanguinity have also been observed in a few diseases in different populations. Although attractive for many reasons, nonconsanguineous marriages will cause risk alleles to spread throughout the population, making most individuals carriers, and ultimately will resume the production of recessive diseases in subsequent generations. Although consanguinity, from an evolutionary point of view, is beneficial at the population level, it increases the risk of diseases in the very next generation. Presently, there is no treatment for most of the genetic disorders; we cannot opt for consanguinity for long-term benefits. Nonconsanguineous marriages are a better strategy by which we may delay disease manifestation for some generations until science offers a viable solution. K E Y W O R D Sconsanguinity, disease allele, evolution, genetic counseling, homozygosity, recessive genetic disorders 214