Novel LIPA mutations in Mexican siblings with lysosomal acid lipase deficiency

Lysosomal acid lipase(LAL) deficiency is an underrecognized lysosomal disease caused by deficient enzymatic activity of LAL.In this report we describe two affected female Mexican siblings with early hepatic complications.At two months of age,the first sibling presented with alternating episodes of diarrhea and constipation,and later with hepatomegaly,elevated transaminases,high levels of total and low-density lipoprotein cholesterol,and low levels of highdensity lipoprotein.Portal hypertension and grade 2 esophageal varices were detected at four years of age.The second sibling presented with hepatomegaly,elevated transaminases and mildly elevated lowdensity lipoprotein and low high-density lipoprotein at six months of age.LAL activity was deficient in both patients.Sequencing of LIPA revealed two previously unreported heterozygous mutations in exon 4:c.253C>A and c.294C>G.These cases highlight the clinical continuum between the so-called Wolman disease and cholesteryl ester storage disease,and underscore that LAL deficiency represents a single disease with a degree of clinical heterogeneity.

Analysis of Linkage for Ten X-STR Markers in a Rio de Janeiro(Brazil)Three-Generation Family Sample

Recently, typing of polymorphisms on the X chromosome has become a standard technique in forensic genetics and a growing number of short tandem repeats (STR) has been established in this chromosome related to genetic population studies. Knowledge of marker recombination is very important especially when the X chromosome typing is used in forensic kinship analysis. It is known that the meiotic recombination is not a simple function of the physical distance between segments of the DNA but the recombination events between them tend to be clustered at special regions of the chromosome. Information on the rate of recombination among markers can be gathered by studying families through several generations. In this work we have typed DNA samples of pedigree consisting of nineteen families in Rio de Janeiro, constituted of grandfather, mother and grandson, and in some cases grandmother and aunt, and reported the recombination of 10 STR markers of the X chromosome. The study of the linkage analysis using the LOD score has shown that the marker pairs DXS8378-DXS7423, DXS7132-DXS9898, DXS7132-GATA172D05 DXS9898-DXS7133 and DXS6809-DXS7133 are not transmitted in a random way, during a recombination event.

Comprehensive Analysis of Pan-African Mitochondrial DNA Variation Provides New Insights into Continental Variation and Demography

Africa is the cradle of all human beings, and although it has been the focus of a number of genetic studies, there are many questions that remain unresolved. We have performed one of the largest and most comprehensive meta-analyses of mitochondrial DNA （mtDNA） lineages carried out in the African continent to date. We generated high-throughput mtDNA single nucleotide polymorphism （SNP） data （230 SNPs） from 2024 Africans, where more than 500 of them were additionally genotyped for the control region. These data were analyzed together with over 12,700 control region profiles collected from the literature, representing more than 300 population samples from Africa. Insights into the African homeland of humans are discussed. Phylogeographic patterns for the African continent are shown at a high phylogeographic resolution as well as at the population and regional levels. The deepest branch of the mtDNA tree, haplogroup L0, shows the highest sub-haplogroup diversity in Southeast and East Africa, suggesting this region as the homeland for modem humans. Several demographic estimates point to the coast as a facilitator of human migration in Africa, but the data indicate complex patterns, perhaps mirroring the effect of recent continental-scaled demographic events in re-shaping African mtDNA variability.