ABSTRACT
Mucopolysaccharidosis (MPS) IVA is a rare autosomal recessive disease with a highly variable distribution worldwide. Discrepancies in the incidence of MPS IVA among populations of different ethnicities are mostly attributed to founder effects. Demographic and clinical data from 28 MPS IVA patients, followed at a single center, and ancestry (Y chromosome and mitochondrial markers) of a subsample of 17 patients, most with the p.Ser341Arg (c.1023C>G) mutation were analyzed. Parental consanguinity was observed in 15/20 couples; a rare homozygous N-acetylgalactosamine-6-sulfatase (GALNS) mutation was found in 7/16 families with intra-familial phenotypic heterogeneity. Paternal ancestry was 94.2% (16/17) European, 5.8% (1/17) African, and 0% Amerindian. The European paternal haplogroups R1a, R1b, and R* accounted for 94.2% (16/17) of the patients. The R1b haplogroup, identified in 59% (10/17) of the patients, is frequently found in populations from the Iberian Peninsula. European, Amerindian, and African maternal ancestry was observed in 46.9% (8/17), 35.4% (6/17), and 17.7% (3/17) of the patients, respectively. Study of a cluster of MPS IVA patients from Northeastern Brazil, with high parental consanguinity and phenotypic heterogeneity showed predominantly European parental ancestry. This ancestry finding corroborates historical data on the local settlement, formed predominantly by European men.
Subject(s)
Chondroitinsulfatases/genetics , Genetic Heterogeneity , Haplotypes/genetics , Mucopolysaccharidosis IV/genetics , Adolescent , Adult , Amino Acid Sequence/genetics , Black People/genetics , Brazil/epidemiology , Child , Chromosomes, Human, Y , Consanguinity , DNA, Mitochondrial/genetics , Demography/statistics & numerical data , Female , Humans , Male , Middle Aged , Mucopolysaccharidosis IV/epidemiology , Mucopolysaccharidosis IV/pathology , Mutation, Missense , Young AdultABSTRACT
The hypothalamic-pituitary-adrenal (HPA) axis is an important hormonal mechanism of the human body and is extremely programmable during embryonic and fetal development. Analyzing its development in this period is the key to understanding in fact how vulnerabilities of congenital diseases occur and any other changes in the phenotypic and histophysiological aspects of the fetus. The environment in which the mother is exposed during the gestational period can influence this axis. Knowing this, our objective was to analyze in recent research the possible impact of epigenetic programming on the HPA axis and its consequences for fetal development. This review brought together articles from two databases: ScienceDirect and PUBMED researched based on key words such as "epigenetics, HPA axis, cardiovascular disease, and circulatory problems" where it demonstrated full relevance in experimental and scientific settings. A total of 101 articles were selected following the criteria established by the researchers. Thus, it was possible to verify that the development of the HPA axis is directly related to changes that occur in the cardiovascular system, to the cerebral growth and other systems depending on the influence that it receives in the period of fetal formation.
