Phenylketonuria mutation analysis in Northern Ireland: a rapid stepwise approach.

We present a multistep approach for the rapid analysis of phenylketonuria (PKU) mutations. In the first step, three common mutations and a polymorphic short tandem repeat (STR) system are rapidly analyzed with a fluorescent multiplex assay. In the second step, minihaplotypes combining STR and VNTR data are used to determine rare mutations likely to be present in an investigated patient, which are then confirmed by restriction enzyme analysis. The remaining mutations are analyzed with denaturant gradient-gel electrophoresis and sequencing. The first two steps together identify both mutations in 90%-95% of PKU patients, and results can be obtained within 2 d. We have investigated 121 Northern Irish families with hyperphenylalaninemia, including virtually all patients born since 1972, and have found 34 different mutations on 241 of the 242 mutant alleles. Three mutations (R408W, I65T, and F39L) account for 57.5% of mutations, while 14 mutations occur with a frequency of 1%-6%. The present analysis system is efficient and inexpensive and is particularly well suited to routine mutation analysis in a diagnostic setting.     

Incidence of the mucopolysaccharidoses in Northern Ireland

An epidemiological study of the mucopolysaccharidoses (MPS) in Northern Ireland using multiple ascertainment sources was carried out and the incidence rate for the period 1958–1985 was estimated. An incidence of approximately 1 in 76 000 live births was obtained for MPS 1H (Hurler phenotype); 1 in 280 000 for MPS 1 H/S (Hurler/Scheie phenotype); 1 in 140 000 live births (1 in 72 000 male live births) for MPS II (Hunter syndrome); 1 in 280 000 for MPS III (Sanfilippo syndrome) and 1 in 76 000 for MPS IV A (Morquio syndrome type A). No cases of MPS IS (Scheie phenotype), MPS IV B (Morquio syndrome type B) or MPS VI (Maroteaux–Lamy syndrome) were ascertained during the study period. Three cases of non-immune hydrops fetalis born to consanguineous parents were thought to be due to β-glucuronidase deficiency (MPS VII) on the basis of placental histology and enzyme studies on both parents but no living cases of MPS VII were ascertained. The overall incidence for all types of mucopolysaccharidosis was approximately 1 in 25 000 live births. A comparison is made with incidence estimates obtained from other published studies. Received: 25 May 1997 / Accepted: 22 August 1997     

Mitochondrial DNA variation in Kets and Nganasans and the early peoples of Northern Eurasia

Mitochondrial DNA (mtDNA) variation was studied in 38 Kets and 24 Nganasans, the indigenous inhabitants of the north of the Yenisey River Basin and the Taimyr Peninsula. The results were compared with the analogous data obtained for 59 Kondinski and 39 Sos'vinski Mansi. As a whole, mitochondrial gene pool of Mansi, Nganasans, and Kets was characterized by unique combination of European-specific (H, H2, H3, H8, U2, U4, U5, U7, J2, and W) and Asian-specific (A, C, D, and Z) mtDNA haplogroups. Specific features of the haplogroup geographical distribution along with the results of phylogenetic reconstruction favor the hypothesis of the genetic trace left in Eastern Cis-Urals and the adjacent Siberian territories by early migrations from the Near East.     

Family size and religious denomination in Northern Ireland

During the summer of 1983, a provincewide representative sample of all ever-married women and single women with children, under the age of 60, was interviewed to examine variations in family size in Northern Ireland. The valuation list of domestic dwellings was used as the sample frame and a clustered sample was drawn from this using the 526 electoral wards as individual clusters. Wards were stratified according to socioeconomic structure, religion, location within Northern Ireland, and whether they were predominatly rural or urban. Sampling within selected clusters was on a systematic basis and proportional to population size. For women currently married, 1 in 5 of the husbands was interviewed using a shorter questionnaire focusing on attitudes to fertility. Of the 3914 houseolds where contact was made and which contained an eligible female, there were 2997 successful interviews with females, giving an effective response rate of 77%. An additional 392 interviews were obtained from husbands. The most persistent fertility differential in Northern Ireland going back at least to the beginning of the 20th century has been that between Protestants and Roman Catholics. According to these preliminary findings, this remains the case. The average number of children born alive to ever-married Roman Catholic females was 3.24 in 1983, compared with 2.29 children for the corresponding group of non-Catholic women. Yet, the survey relates to an instant during a peirod of considerable flux in Roman Catholic fertliity, and comparison of these 1983 data with those collected at the 1971 census of population shows that Roman Catholic family size declined by 11% over the intervening 12 years, although this is marginally reduced after standardization for changes in the age structure of ever-married women. Non-Catholic family size, by contrast, remained virtually static during the same time period. The pace of change has been more pronounced in Belfast and its suburbs. Data are not yet available from the survey to chart these processes by marriage cohort, but some pointers can be obtained from the tabulation of family size by denomination and age of mother. With the exception of the under-20 age group, the average size of Roman Catholic families was consistently and substantially larger than that of the corresponding non-Catholic age group. The absolute difference in terms of mean numbers of children widened steadily with increasing age. These preliminary data also show that there is still a strong geographical dimension to the religious differential in fertility. Average family size was larger in rural than urban areas but moreso for Roman Catholics (16% larger) than for non-Catholics (9% larger). Although differences in family size between Roman Catholics and non-Catholics still prevail, there has been a considerable degree of overall convergence since 1971.