Spinocerebellar ataxia type 10 and Huntington disease-like 2 in Venezuela: Further evidence of two different ancestral founder effects.

INTRODUCTION: The American continent populations have a wide genetic diversity, as a product of the admixture of three ethnic groups: Amerindian, European, and African Sub-Saharan. Spinocerebellar ataxia type 10 (SCA10) and Huntington disease-like 2 (HDL2) have very ancient ancestral origins but are restricted to two populations: Amerindian and African Sub-Saharan, respectively. This study aimed to investigate the genetic epidemiological features of these diseases in Venezuela. METHODS: In-phase haplotypes with the expanded alleles were established in seven unrelated index cases diagnosed with SCA10 and in 11 unrelated index cases diagnosed with HDL2. The origins of remote ancestors were recorded. RESULTS: The geographic origin of the ancestors showed grouping in clusters. SCA10 had a minimal general prevalence of 1:256,174 families in the country, but within the identified geographic clusters, the prevalence ranged from 5 per 100,000 to 43 per 100,000 families. HDL2 had a general prevalence of 1:163,016 families, however, within the clusters, the prevalence ranged from 31 per 100,000 to 60 per 100,000 families. The locus-specific haplotype shared by all families worldwide, including the Venezuelans, supports a single old ancestral origin in each case. CONCLUSION: Knowing the genetic ancestry and geographic origins of patients in Ibero-American mixed populations could have significant diagnostic implications; thus, both diseases in Venezuela should always be first explored in patients with a suggestive phenotype and ancestors coming from the same known geographic clusters.

Dengue seroprevalence and its socioeconomic determinants in Faisalabad, Pakistan: a cross-sectional study

Abstract INTRODUCTION: Socioeconomic disparities in the community make some groups more vulnerable to dengue infection. METHODS: Fourteen dengue cases (IgM positive) served as index cases for the positive geographic cluster investigations. RESULTS: Of 292 individuals, the overall dengue seroprevalence was 22.9% (IgM positive 4.8%; IgG positive 18.1%). The highest (45%) seroprevalence was reported in the most socioeconomically vulnerable lower class, followed by the middle class (39%). Orthogonal comparisons showed that socioeconomic factors play a significant role in the prevalence of dengue. CONCLUSIONS: An integrated approach is required to control the menace through vector control strategies and improvement of socioeconomic conditions.

Geographic clusters of congenital anomalies in Argentina.

Geographical clusters are defined as the occurrence of an unusual number of cases higher than expected in a given geographical area in a certain period of time. The aim of this study was to identify potential geographical clusters of specific selected congenital anomalies (CA) in Argentina. The cases were ascertained from 703,325 births, examined in 133 maternity hospitals in the 24 provinces of Argentina. We used the spatial scan statistic to determine areas of Argentina which had statistically significant elevations of prevalence. Prenatal diagnosis followed by referral of high-risk pregnancies to high complexity hospitals in a hospital-based surveillance system can create artifactual clusters. We assessed the referral bias by evaluating the prevalence heterogeneity within each cluster. Eight clusters of selected CAs with unusually high birth prevalence were identified: anencephaly, encephalocele, spina bifida, diaphragmatic hernia, talipes equinovarus, omphalocele, Cleft lip with or without cleft palate (CL/P), and Down syndrome. The clusters of Down syndrome and CL/P observed in this study match the previously reported clusters. These findings support local targeted interventions to lower the prevalence of the CAs and/or further research on the cause of each cluster. The clusters of spina bifida, anencephaly, encephalocele, omphalocele, congenital diaphragmatic hernia, and talipes equinovarus may be influenced by prenatal diagnosis and referral to high complexity hospitals.

Altitude as a risk factor for the development of hypospadias. Geographical cluster distribution analysis in South America.

OBJECTIVE: Hypospadias is the most common congenital anomaly affecting the genitals. It has been established as a multifactorial disease with increasing prevalence. Many risk factors have been identified such as prematurity, birth weight, mother's age, and exposure to endocrine disruptors. In recent decades multiple authors using surveillance systems have described an increase in prevalence of hypospadias, but most of the published literature comes from developed countries in Europe and North America and few of the published studies have involved cluster analysis. Few large-scale studies have been performed addressing the effect of altitude and other geographical aspects on the development of hypospadias. Acknowledging this limitation, we present novel results of a multinational spatial scan statistical analysis over a 30-year period in South America and an altitude analysis of hypospadias distribution on a continent level. METHOD: A retrospective review was performed of the Latin American collaborative study of congenital malformations (ECLAMC). A total of 4,020,384 newborns was surveyed between 1982 and December 2011 in all participating centers. We selected all patients with hypospadias. All degrees of clinical severity were included in the analysis. Each participating center was geographically identified with its coordinates and altitude above sea level. A spatial scan statistical analysis was performed using Kulldorf's methodology and a prevalence trend analysis over time in centers below and above 2000 m. RESULTS: During the study period we found 159 hospitals in six different countries (Colombia, Bolivia, Brazil, Argentina, Chile, and Uruguay) with 4,537 cases of hypospadias and a global prevalence rate of 11.3/10,000 newborns. Trend analysis showed that centers below 2000 m had an increasing trend with an average of 10/10,000 newborns as opposed to those centers above 2000 m that showed a reducing trend with an average prevalence of 7.8 (p = 0.1246). We identified clusters with significant increases of prevalence in five centers along the coast at an average altitude of 219.8 m above sea level (p > 0.0000). Reduction in prevalence was found in clusters located in two centers on the Andes mountains. Altitude of 2,000 m was associated with hypospadias (Figure), with an OR 0.59 (0.5-0.69). There are ethnic arguments to support our results supported by protective polymorphism distribution in high lands. CONCLUSION: Altitude above 2,000 m is suggested to have a protective effect for hypospadias. Specific clusters have been identified with increased risk for hypospadias. Environmental risk factors in these areas need to be further studied given the association seen between altitude and the distribution of more severe cases.

Sirenomelia in Argentina: Prevalence, geographic clusters and temporal trends analysis.

BACKGROUND: Sirenomelia is a severe malformation of the lower body characterized by a single medial lower limb and a variable combination of visceral abnormalities. Given that Sirenomelia is a very rare birth defect, epidemiological studies are scarce. The aim of this study is to evaluate prevalence, geographic clusters and time trends of sirenomelia in Argentina, using data from the National Network of Congenital Anomalies of Argentina (RENAC) from November 2009 until December 2014. METHODS: This is a descriptive study using data from the RENAC, a hospital-based surveillance system for newborns affected with major morphological congenital anomalies. We calculated sirenomelia prevalence throughout the period, searched for geographical clusters, and evaluated time trends. RESULTS: The prevalence of confirmed cases of sirenomelia throughout the period was 2.35 per 100,000 births. Cluster analysis showed no statistically significant geographical aggregates. Time-trends analysis showed that the prevalence was higher in years 2009 to 2010. CONCLUSION: The observed prevalence was higher than the observed in previous epidemiological studies in other geographic regions. We observed a likely real increase in the initial period of our study. We used strict diagnostic criteria, excluding cases that only had clinical diagnosis of sirenomelia. Therefore, real prevalence could be even higher. This study did not show any geographic clusters. Because etiology of sirenomelia has not yet been established, studies of epidemiological features of this defect may contribute to define its causes. Birth Defects Research (Part A) 106:604-611, 2016. © 2016 Wiley Periodicals, Inc.

Genealogical data in population medical genetics: Field guidelines.

This is a guide for fieldwork in Population Medical Genetics research projects. Data collection, handling, and analysis from large pedigrees require the use of specific tools and methods not widely familiar to human geneticists, unfortunately leading to ineffective graphic pedigrees. Initially, the objective of the pedigree must be decided, and the available information sources need to be identified and validated. Data collection and recording by the tabulated method is advocated, and the involved techniques are presented. Genealogical and personal information are the two main components of pedigree data. While the latter is unique to each investigation project, the former is solely represented by gametic links between persons. The triad of a given pedigree member and its two parents constitutes the building unit of a genealogy. Likewise, three ID numbers representing those three elements of the triad is the record field required for any pedigree analysis. Pedigree construction, as well as pedigree and population data analysis, varies according to the pre-established objectives, the existing information, and the available resources.