Background: Mutations in the MECP2 gene have been recently identified as the cause of Rett syndrome, prompting research into genotype-phenotype relations. However, despite these genetic advances there has been little descriptive epidemiology of the full range of phenotypes. Aims: To describe the variation in phenotype in Rett syndrome using four different scales, by means of a population database. Methods: Using multiple sources of ascertainment including the Australian Paediatric Surveillance Unit, the development of an Australian cohort of Rett syndrome cases born since 1976 has provided the first genetically characterised population based study of Rett syndrome. Follow up questionnaires were administered in 2000 to families and used to provide responses for items in four different severity scales. Results: A total of 199 verified cases of Rett syndrome were reported between January 1993 and July 2000; 152 families provided information for the follow up study. The mean score using the Kerr scale was 22.9 (SD 4.8) and ranged from 20.5 in those under 7 years to 24.2 in those over 17 years. The mean Percy score was 24.9 (SD 6.6) and also increased with age group from 23.0 to 26.9. The mean Pineda score was 16.3 (SD 4.5) and did not differ by age group. The mean WeeFIM was 29.0 (SD 11.9), indicating extreme dependence, and ranged from 18 to 75. Conclusion: We have expanded on the descriptive epidemiology of Rett syndrome and shown different patterns according to the severity scale selected. Although all affected children are severely functionally dependent, it is still possible to identify some variation in ability, even in children with identified MECP2 mutations.

Polycystin-1 and polycystin-2 are the products of PKD1 and PKD2, genes that are mutated in most cases of autosomal dominant polycystic kidney disease. Polycystin-2 shares ϳ46% homology with pore-forming domains of a number of cation channels. It has been suggested that polycystin-2 may function as a subunit of an ion channel whose activity is regulated by polycystin-1. Here we report the identification of a human gene, PKDL, which encodes a new member of the polycystin protein family designated polycystin-L. Polycystin-L has 50% amino acid sequence identity and 71% homology to polycystin-2 and has striking sequence and structural resemblance to the pore-forming ␣1 subunits of Ca 2؉ channels, suggesting that polycystin-L may function as a subunit of an ion channel. The full-length transcript of PKDL is expressed at high levels in fetal tissues, including kidney and liver, and down-regulated in adult tissues. PKDL was assigned to 10q24 by fluorescence in situ hybridization and is linked to D10S603 by radiation hybrid mapping. There is no evidence of linkage to PKDL in six ADPKD families that are unlinked to PKD1 or PKD2. The mouse homologue of PKDL is deleted in Krd mice, a deletion mutant with defects in the kidney and eye. We propose that PKDL is an excellent candidate for as yet unmapped cystic diseases in man and animals.Polycystin-1 and polycystin-2 are the respective gene products of PKD1 and PKD2, mutations in which account for ϳ95% of cases of ADPKD.1 ADPKD affects up to 1/1,000 individuals and is associated with a 50% incidence of end-stage renal failure by the sixth decade of life (1). At least one additional gene is known to be mutated in the ADPKD population (2, 3) but has yet to be identified.Polycystin-1 encodes a 4,303-amino acid plasma membrane protein with a large extracellular N-terminal domain that contains leucine-rich repeats, a C-type lectin domain, and an LDL-A-like domain, all three of which are involved in cell-cell or cell-matrix interactions in other proteins (4 -6). These domains are followed by 16 repeats of the so-called PKD domain and by an REJ (receptor for egg jelly in sea urchin sperm)-like domain. Polycystin-1 has 7 to 11 transmembrane domains. The short cytoplasmic tail (197 amino acids) of polycystin-1 contains a coiled-coil domain, which appears to interact with other proteins containing similar structures (7,8).The predicted amino acid sequence of the PKD2 gene is homologous to the C terminus of polycystin-1 (9, 10). Polycystin-2 is a 968-amino acid protein with ϳ46% sequence similarity to each domain of the pore-forming ␣1 subunits of Ca 2ϩ and other cation channels, and like these channel subunits, it is predicted to have six transmembrane domains. Polycystin-2 has a putative Ca 2ϩ binding structure (EF-hand) in its Cterminal cytoplasmic domain. It interacts biochemically with polycystin-1 and with itself (7,8).Here we report the identification, chromosomal localization, and expression of a third gene encoding a protein of the polycystin family. The product of this gene is ...

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ACE is not likely to play a role as a determinant of ADPKD phenotype severity.