Biotinidase deficiency: novel mutations in Algerian patients.

Biotinidase deficiency is an autosomal recessive disorder of biotin metabolism leading to varying degrees of neurologic and cutaneous symptoms when untreated. In the present study, we report the clinical features and the molecular investigation of biotinidase deficiency in four unrelated consanguineous Algerian families including five patients with profound biotinidase deficiency and one child characterized as partial biotinidase deficiency. Mutation analysis revealed three novel mutations, c.del631C and c.1557T>G within exon 4 and c.324-325insTA in exon 3. Since newborn screening is not available in Algeria, cascade screening in affected families would be very helpful to identify at risk individuals.

The experience of a Tunisian referral centre in prenatal diagnosis of Xeroderma pigmentosum.

AIMS: Xeroderma pigmentosum (XP, OMIM 278700-278780) is one of the most severe genodermatoses and is relatively frequent in Tunisia. In the absence of any therapy and to better manage the disease, we aimed to develop a molecular tool for DNA-based prenatal diagnosis. METHODS: Six consanguineous Tunisian XP families (4 XP-A and 2 XP-C) have benefited from a prenatal diagnosis. Screening for mutations was performed by direct sequencing, while maternal-foetal contamination was checked by genotyping. RESULTS: Among the 7 prenatal diagnoses, 4 foetuses were heterozygous for the screened mutation. Exclusion of contamination by maternal cells was checked. Mutations were detected at a homozygous state in the remaining cases, and the parents decided to terminate pregnancy. CONCLUSION: Our study illustrates the implementation of prenatal diagnosis for better health support of XP in Tunisia.

Severe phenotypes in two Tunisian families with novel XPA mutations: evidence for a correlation between mutation location and disease severity.

Xeroderma pigmentosum (XP) is a rare disorder characterized by a high skin sun-sensitivity predisposing to skin cancers at an early age. Among Tunisian XP patients with an intermediate skin phenotype, 92% presented neurological abnormalities related to XPA gene deficiency. Clinical variability of the XP-A phenotype is associated with a mutational heterogeneity. In the present study, two Tunisian families with severe dermatological and neurological XP phenotypes were investigated in order to determine clinical characteristics and genetic basis. Two Tunisian families with four XP affected children were examined in the Dermatology Department. Clinical features showed severe presentation of the disease. Coding regions of the XPA gene were analysed by direct sequencing. Results showed the presence of a novel mutation, p.E111X, in three patients belonging to the same family and presenting a very severe phenotype i.e. development of skin lesions and neurological signs before 1 year age. For the other patient, we identified a nonsense mutation, p.R207X, already identified in a Palestinian XP-A patient. Identification of novel causing mutations in Tunisian XP-A patients shows the genetic and mutational heterogeneity of the disease in Tunisia. Despite a relatively homogenous mutational spectrum, mutational heterogeneity for rare cases is observed because of the high rate of consanguinity.

Identification of a primarily neurological phenotypic expression of xeroderma pigmentosum complementation group A in a Tunisian family.

Xeroderma pigmentosum (XP) is a rare genodermatosis predisposing to skin cancers. The disease is classified into eight groups. Among them, XP group A (XP-A) is characterized by the presence of neurological abnormalities in addition to cutaneous symptoms. In the present study, we report a particular family with XP-A in which some members showed an atypical clinical presentation, i.e. unexplained neurological abnormalities with discrete skin manifestations. Molecular investigation allowed identification of a novel XPA mutation and complete phenotype-genotype correlation for this new phenotypic expression of XP-A.

Mitochondrial DNA sequence diversity in a sedentary population from Egypt.

The mitochondrial DNA (mtDNA) diversity of 58 individuals from Upper Egypt, more than half (34 individuals) from Gurna, whose population has an ancient cultural history, were studied by sequencing the control-region and screening diagnostic RFLP markers. This sedentary population presented similarities to the Ethiopian population by the L1 and L2 macrohaplogroup frequency (20.6%), by the West Eurasian component (defined by haplogroups H to K and T to X) and particularly by a high frequency (17.6%) of haplogroup M1. We statistically and phylogenetically analysed and compared the Gurna population with other Egyptian, Near East and sub-Saharan Africa populations; AMOVA and Minimum Spanning Network analysis showed that the Gurna population was not isolated from neighbouring populations. Our results suggest that the Gurna population has conserved the trace of an ancestral genetic structure from an ancestral East African population, characterized by a high M1 haplogroup frequency. The current structure of the Egyptian population may be the result of further influence of neighbouring populations on this ancestral population.

[World Population Day, July 1997. For a trilogy in symbiosis]. / Journee Mondiale de la Population, Juillet 1997. Pour une trilogie en symbiose.

PIP: World population growth was very slow throughout most of history, with the 1 billion mark attained only in the 19th century. Total world population reached 5.848 billion in 1997, and at a growth rate of 1.4% is expected to reach 8 billion in 2025. Over 80% of the growth occurs in developing countries. Asia, with 3.538 billion, remains the most populous continent. 1.243 billion are in China; 960 million, in India. Population growth appears to be declining everywhere in the world expect Africa, which is growing at 2.6%, and Western Asia, growing at 2.2%. The growth rate is 0.3% in industrialized countries as a whole, and 0% in Europe. The developing countries have crude birth and death rates of 29/1000 and 9/1000, respectively, compared to 12/1000 and 10/1000 in developed countries. Life expectancy at birth is 63 in developing countries, 50 in East and Central Africa, and 74 in the industrialized countries. Nearly all regions have entered the demographic transition, but they are at very different stages. As demographic trends diverge, the gap in economic development between developed and developing countries is widening. According to the 1996 World Report on Human Development, only 21.7% of the world's gross national product originates in developing countries. The differences are enormous in the degree of satisfaction of basic socioeconomic and health needs. It has become clear that demographic pressure is a determining factor in environmental degradation. Climatic disturbances, water pollution, deforestation and desertification attest to overconsumption of resources and emission of enormous quantities of wastes. Policies to control demographic growth have become the pivot of processes for construction of healthy societies. All studies have shown that issues of population, resources, and the environment are organically linked. Tunisia, a progressive country, has been concerned since independence with economic growth and social advancement of the population, and population has been integrated into the different social and economic plans. Economic conditions have improved, and the principal demographic and health parameters are increasingly under control. Tunisia has achieved a contraceptive prevalence rate of 60%.^ieng