Molecular monitoring of myelodysplastic neoplasm: Don't just watch this space, consider the patient's ancestry.

The heterogeneity of Myelodysplastic Neoplasm (MDS) extends beyond mutational diversity to include significant ethnic variability, a factor that has been underexplored. While the development of the IPSS-M prognostic tool has advanced our understanding of MDS, its reliance on data primarily from European cohorts limits its applicability to non-European populations. Duployez et al.'s review highlighted the importance of molecular markers in MDS for personalized treatment and disease monitoring yet did not address the impact of genetic ancestry. This commentary critiques the IPSS-M's limited sample of 110 Brazilian patients, questioning its adequacy in reflecting the influence of patient ancestry on prognostic accuracy. Given the potential for differing mutation profiles and prognostic implications across diverse ethnic groups, robust genomic ancestry studies are urgently needed. These studies should stratify MDS patients by ethnic background to investigate mutation incidence and impacts, thereby validating IPSS-M and potentially identifying new prognostic markers. Incorporating ethnic diversity into prognostic models is essential for ensuring they are truly universal and inclusive, thereby improving personalized treatment and care for all MDS patients. Commentary on: Duployez and Preudhomme. Monitoring molecular changes in the management of myelodysplastic syndromes. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19614.

Genomic analysis of an Ecuadorian individual carrying an SCN5A rare variant.

BACKGROUND: Ion channels, vital transmembrane protein complexes, regulate ion movement within cells. Germline variants in channel-encoding genes lead to channelopathies. The sodium channels in cardiac cells exhibit a structure of an alpha subunit and one to two beta subunits. The alpha subunit, encoded by the SCN5A gene, comprises four domains. CASE PRESENTATION: A fifteen-year-old Ecuadorian female with atrial flutter and abnormal sinus rhythm with no familial history of cardiovascular disease underwent NGS with the TruSight Cardio kit (Illumina). A likely pathogenic SCN5A gene variant (NM_188056.2:c.2677 C > Tp. Arg893Cys) was identified, associated with arrhythmias, long QT, atrial fibrillation, and Brugada syndrome. Ancestral analysis revealed a predominant European component (43.9%), followed by Native American (35.7%) and African (20.4%) components. CONCLUSIONS: The participant presents atrial flutter and conduction disorders, despite lacking typical cardiovascular risk factors. The proband carries a SCN5A variant that has not been previously reported in Latin America and may be associated to her phenotype. The documented arginine-to-cysteine substitution at position 893 in the protein is crucial for various cellular functions. The subject's mixed genetic composition highlights potential genetic contributors to atrial flutter, emphasizing the need for comprehensive genetic studies, particularly in mixed populations like Ecuadorians. This case underscores the importance of genetic analysis for personalized treatment and the significance of studying diverse genetic backgrounds in understanding cardiovascular diseases.

Joint models reveal genetic architecture of pubertal stage transitions and their association with BMI in admixed Chilean population.

Early or late pubertal onset can lead to disease in adulthood, including cancer, obesity, type 2 diabetes, metabolic disorders, bone fractures, and psychopathologies. Thus, knowing the age at which puberty is attained is crucial as it can serve as a risk factor for future diseases. Pubertal development is divided into five stages of sexual maturation in boys and girls according to the standardized Tanner scale. We performed genome-wide association studies (GWAS) on the "Growth and Obesity Chilean Cohort Study" cohort composed of admixed children with mainly European and Native American ancestry. Using joint models that integrate time-to-event data with longitudinal trajectories of body mass index (BMI), we identified genetic variants associated with phenotypic transitions between pairs of Tanner stages. We identified $42$ novel significant associations, most of them in boys. The GWAS on Tanner $3\rightarrow 4$ transition in boys captured an association peak around the growth-related genes LARS2 and LIMD1 genes, the former of which causes ovarian dysfunction when mutated. The associated variants are expression and splicing Quantitative Trait Loci regulating gene expression and alternative splicing in multiple tissues. Further, higher individual Native American genetic ancestry proportions predicted a significantly earlier puberty onset in boys but not in girls. Finally, the joint models identified a longitudinal BMI parameter significantly associated with several Tanner stages' transitions, confirming the association of BMI with pubertal timing.

Genetic Ancestry and Self-Reported "Skin Color/Race" in the Urban Admixed Population of São Paulo City, Brazil.

Epidemiological studies frequently classify groups based on phenotypes like self-reported skin color/race, which inaccurately represent genetic ancestry and may lead to misclassification, particularly among individuals of multiracial backgrounds. This study aimed to characterize both global and local genome-wide genetic ancestries and to assess their relationship with self-reported skin color/race in an admixed population of Sao Paulo city. We analyzed 226,346 single-nucleotide polymorphisms from 841 individuals participating in the population-based ISA-Nutrition study. Our findings confirmed the admixed nature of the population, demonstrating substantial European, significant Sub-Saharan African, and minor Native American ancestries, irrespective of skin color. A correlation was observed between global genetic ancestry and self-reported color-race, which was more evident in the extreme proportions of African and European ancestries. Individuals with higher African ancestry tended to identify as Black, those with higher European ancestry tended to identify as White, and individuals with higher Native American ancestry were more likely to self-identify as Mixed, a group with diverse ancestral compositions. However, at the individual level, this correlation was notably weak, and no deviations were observed for specific regions throughout the individual's genome. Our findings emphasize the significance of accurately defining and thoroughly analyzing race and ancestry, especially within admixed populations.

Social determinants of health but not global genetic ancestry predict dementia prevalence in Latin America.

INTRODUCTION: Leveraging the nonmonolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aim to evaluate the relative contributions of SDoH and genetic ancestry in predicting dementia prevalence in Latin American populations. METHODS: Community-dwelling participants aged 65 and older (N = 3808) from Cuba, Dominican Republic, Mexico, and Peru completed the 10/66 protocol assessments. Dementia was diagnosed using the cross-culturally validated 10/66 algorithm. Multivariate linear regression models adjusted for SDoH were used in the main analysis. This study used cross-sectional data from the 1066 population-based study. RESULTS: Individuals with higher proportions of Native American (>70%) and African American (>70%) ancestry were more likely to exhibit factors contributing to worse SDoH, such as lower educational levels (p < 0.001), lower socioeconomic status (p < 0.001), and higher frequency of vascular risk factors (p < 0.001). After adjusting for measures of SDoH, there was no association between ancestry proportion and dementia probability, and ancestry proportions no longer significantly accounted for the variance in cognitive performance (African predominant p = 0.31 [-0.19, 0.59] and Native predominant p = 0.74 [-0.24, 0.33]). DISCUSSION: The findings suggest that social and environmental factors play a more crucial role than genetic ancestry in predicting dementia prevalence in Latin American populations. This underscores the need for public health strategies and policies that address these social determinants to effectively reduce dementia risk in these communities. HIGHLIGHTS: Countries in Latin America express a large variability in social determinants of health and levels of admixture. After adjustment for downstream societal factors linked to SDoH, genetic ancestry shows no link to dementia. Population ancestry profiles alone do not influence cognitive performance. SDoH are key drivers of racial disparities in dementia and cognitive performance.

Genetic determinants of serum bilirubin using inferred native American gene variants in Chilean adolescents.

Gene variants in the UGT1A1 gene are strongly associated with circulating bilirubin levels in several populations, as well as other variants of modest effect across the genome. However, the effects of such variants are unknown regarding the Native American ancestry of the admixed Latino population. Our objective was to assess the Native American genetic determinants of serum bilirubin in Chilean admixed adolescents using the local ancestry deconvolution approach. We measured total serum bilirubin levels in 707 adolescents of the Chilean Growth and Obesity Cohort Study (GOCS) and performed high-density genotyping using the Illumina-MEGA array (>1.7 million genotypes). We constructed a local ancestry reference panel with participants from the 1000 Genomes Project, the Human Genome Diversity Project, and our GOCS cohort. Then, we inferred and isolated haplotype tracts of Native American, European, or African origin to perform genome-wide association studies. In the whole cohort, the rs887829 variant and others near UGT1A1 were the unique signals achieving genome-wide statistical significance (b = 0.30; p = 3.34 × 10-57). After applying deconvolution methods, we found that significance is also maintained in Native American (b = 0.35; p = 3.29 × 10-17) and European (b = 0.28; p = 1.14 × 10-23) ancestry components. The rs887829 variant explained a higher percentage of the variance of bilirubin in the Native American (37.6%) compared to European ancestry (28.4%). In Native American ancestry, carriers of the TT genotype of this variant averaged 4-fold higher bilirubinemia compared to the CC genotype (p = 2.82 × 10-12). We showed for the first time that UGT1A1 variants are the primary determinant of bilirubin levels in Native American ancestry, confirming its pan-ethnic relevance. Our study illustrates the general value of the local ancestry deconvolution approach to assessing isolated ancestry effects in admixed populations.

Personalized nutrition: the end of the one-diet-fits-all era.

Personalized Nutrition emerged as a new trend for providing nutritional and food advice based on the individual's genetic composition, a field driven by the advancements in the multi-omic sciences throughout the last century. It intends not only to tailor the recommended daily allowances of nutrients and functional foods that a person may need but also to maintain the principles of sustainability and eco-friendliness. This principle implies the implementation of strategies within the healthcare system to advocate for the ending of the one-diet-fits-all paradigm by considering a personalized diet as an ally to prevent diet-related chronic diseases. In this Perspective, we highlight the potential benefits of such a paradigm within the region of Latin America, particularly Mexico, where the genetic admixture of the population, food biodiversity, and food culture provide unique opportunities to establish personalized nutrigenetic strategies. These strategies could play a crucial role in preventing chronic diseases and addressing the challenges confronted in the region.

Dominance of African racial ancestry in honey bee colonies of Mexico 30 years after the migration of hybrids from South America.

The Africanized honey bee, a hybrid of Apis mellifera scutellata from Africa with European subspecies, has been considered an invasive species and a problem for beekeeping. Africanized bees arrived in Mexico in 1986, 30 years after their accidental release in Brazil. Although government programs were implemented for its eradication, Africanized populations persist in Mexico, but precise information on the patterns of genetic introgression and racial ancestry is scarce. We determined maternal and parental racial ancestry of managed and feral honey bees across the five beekeeping regions of Mexico, using mitochondrial (mtDNA, COI-COII intergenic region) and nuclear markers (94 ancestrally informative SNPs), to assess the relationship between beekeeping management, beekeeping region, altitude, and latitude with the distribution of maternal and parental racial ancestry. Results revealed a predominantly African ancestry in the Mexican honey bees, but the proportion varied according to management, beekeeping regions, and latitude. The Mexican honey bees showed 31 haplotypes of four evolutionary lineages (A, M, C, and O). Managed honey bees had mitochondrial and nuclear higher proportions of European ancestry than feral honey bees, which had a higher proportion of African ancestry. Beekeeping regions of lower latitudes had higher proportions of African nuclear ancestry. Managed and feral honey bees showed differences in the proportion of maternal and nuclear racial ancestry. Managed honey bees from the Yucatan Peninsula and feral honey bees had a higher mtDNA than nuclear proportions of African ancestry. Managed honey bees, except those on the Yucatan Peninsula, had a higher nuclear than mtDNA proportion of African ancestry. Our study demonstrates that Africanized honey bee populations are genetically diverse and well established in Mexico, which highlights the limitations of management and government programs to contain the Africanization process and demands the incorporation of this lineage in any breeding program for sustainable beekeeping.

Genomic ancestry and cancer among Latin Americans.

Latin American populations, characterized by intricate admixture patterns resulting from the intermingling of ancestries from European, Native American (NA) Asian, and African ancestries which result in a vast and complex genetic landscape, harboring unique combinations of novel variants. This genetic diversity not only poses challenges in traditional population genetics methods but also opens avenues for a deeper understanding of its implications in health. In cancer, the interplay between genetic ancestry, lifestyle factors, and healthcare disparities adds a layer of complexity to the varying incidence and mortality rates observed across different Latin American subpopulations. This complex interdependence has been unveiled through numerous studies, whether conducted on Latin American patients residing on the continent or abroad, revealing discernible differences in germline composition that influence divergent disease phenotypes such as higher incidence of Luminal B and Her2 breast tumors, EGFR and KRAS mutated lung adenocarcinomas in addition to an enrichment in BRCA1/2 pathogenic variants and a higher than expected prevalence of variants in colorectal cancer associated genes such as APC and MLH1. In prostate cancer novel risk variants have also been solely identified in Latin American populations. Due to the complexity of genetic divergence, inputs from each individual ancestry seem to carry independent contributions that interplay in the development of these complex disease phenotypes. By understanding these unique population characteristics, genomic ancestries hold a promising avenue for tailoring prognostic assessments and optimizing responses to oncological interventions.

The socio-colonial history of Surinamese surnames applied to a validated surname list to identify ancestry in health research.

Around half of the population of Suriname, who are mainly of African and South Asian descent, migrated to the Netherlands at the end of the previous century, where they face higher perinatal and maternal mortality and up to 5 years lower life expectancy than European-Dutch. Analyses by ancestry are needed to address these inequalities, but the law prohibits registration by ancestry. Therefore, a list of Surinamese surnames was compiled and validated to identify the largest groups, African-Surinamese or South Asian-Surinamese ancestry in health research. A complete database of Surinamese surnames was provided by the National Population Registry of Suriname. Surname recognition by researchers of Surinamese ancestry was used. Disagreement was resolved using historical registers and through discussion. The list was further validated against contemporary lists of Surinamese surnames with self-defined ancestry, obtained during population and clinical studies in Suriname and the Netherlands. All 71,529 Surinamese surnames were encoded, as African-Surinamese (34%), South Asian-Surinamese (18%), Brazilian or other Iberian (17%), Indonesian-Surinamese (13%), Chinese-Surinamese (5%), First Nation (2%), and other (10%). Compared to self-defined ancestry, South Asian-Surinamese surname coding had 100% sensitivity, 99.8% specificity, and 99.9% accuracy. For African-Surinamese, who may have Dutch surnames, these values depended on geocoding. With a known Surinamese origin, sensitivity, specificity, and accuracy were, respectively, 97.3%, 100%, and 98.6%, but without this information, there was interference of African-Surinamese with European-Dutch surnames in the Dutch validation sample. In conclusion, the Surinamese Surname List has a high accuracy in identifying persons of Surinamese ancestry. This quick, inexpensive, and nonintrusive method, which is unaffected by response bias, might be a valuable tool in public health research to help address the profound health disparities by ancestry.

Genetic ancestry and radical prostatectomy findings in Hispanic/Latino patients.

Background: African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. Patients and methods: We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry Informative Markers. We examined the associations of the genetic ancestry components with the Gleason Grade Groups (GG) and the clinicopathological characteristics. Results: No association was observed between the genetic ancestry with the biochemical recurrence or Gleason GG; however, in a two groups comparison, there were statistically significant differences between GG3 and GG4/GG5 for European ancestry, with a higher mean ancestry proportion in GG4/GG5. A lower risk of being diagnosed at an advanced age was observed for patients with high African ancestry than those with low African ancestry patients (OR: 0.96, CI: 0.92-0.99, p=0.03). Conclusion: Our findings revealed an increased risk of presentation of PC at an earlier age in patients with higher African ancestry compared to patients with lower African ancestry in our Hispanic/Latino patients.

Pharmacogenomic implications of the differential distribution of CYP3A5 metabolic phenotypes among Latin American populations.

This study shows that the distribution of CYP3A5 alleles (*1, *3, *6 and *7) and genotype-predicted CYP3A5 phenotypes vary significantly across Latin American cohorts (Brazilians and the One Thousand Genomes Admixed American superpopulation), as well as among subcohorts comprising individuals with the highest proportions of Native, European or sub-Saharan African ancestry. Differences in biogeographical ancestry across the study groups are the likely explanation for these results. The differential distribution of CYP3A5 phenotypes has major pharmacogenomic implications, affecting the proportion of individuals carrying high risk CYP3A5 phenotypes for the immunosuppressant tacrolimus and the number of patients that would need to be genotyped to prevent acute rejection in kidney transplant recipients under tacrolimus treatment.

HLA allelic diversity in the Waorani population of Ecuador: Its significance to their ancestry and migration.

The Waorani, an isolated indigenous tribe in Ecuador, have long been characterized by limited genetic diversity, with few studies delving into their genetic background. Human Leukocyte Antigen (HLA) genes which are located in the human major histocompatibility complex (MHC) provides valuable insights into population evolution due to its highly polymorphic nature. However, little is known about the HLA diversity and ancestry of the Waorani population. In this study, we sequenced eight HLA genes using Next Generation Sequencing (NGS) from 134 Waorani individuals and obtained up to four-field HLA allele resolution. Cluster and phylogenetic analysis show that the Waorani are genetically distant from other Ecuador populations, but instead show genetic affinities with the Puyanawa and Terena tribes from Brazil, as well as the Mixe tribe from Mexico. The identification of alleles common within the Waorani population, previously linked to specific health conditions, notably paves the way for future association analyses. This extensive study, employing Next-Generation Sequencing (NGS) technology, significantly enriches the sparse and segmented understanding of HLA diversity in the South American region. Our findings enhance the global comprehension of human genetic diversity and underscore the value of studying indigenous populations. Such research is vital for deepening our insights into human migration patterns and evolutionary processes.

NUDT15 and TPMT polymorphisms in three distinct native populations of the Brazilian Amazon.

This is the first report of the distribution of TPMT and NUDT15 single nucleotide polymorphisms and metabolic phenotypes associated with cytotoxicity of thiopurine drugs, in indigenous groups of Brazilian Amazon: Munduruku, Paiter-Suruí and Yanomami. The minor allele frequency (MAF) of NUDT15 rs116855232 did not differ significantly across the groups; TPMT rs1800462 was absent, while rs1800460 and rs1142345 were in strong linkage disequilibrium, and 10- and 30-fold more common in Paiter-Suruí. Indeed, the MAFs in Paiter-Surui (0.193 and 0.188) are the largest report globally. The distribution of combined NUDT15/TPMT metabolic phenotypes differed significantly (p < 0.0001) and largely (Cramér´s V = 0.37) across cohorts. This has important pharmacogenetic implications: the Clinical Pharmacogenetics Implementation Consortium recommendations to reduce or consider reduction of thiopurine dose applies to 4.4% Yanomami, 5.6% Munduruku, versus 41% Paiter-Suruí. The proportion of Paiter-Suruí at risk of thiopurine intolerance is 3- to 4-fold higher than any other population worldwide.

Exploring SoySNP50K and USDA Germplasm Collection Data to Find New QTLs Associated with Protein and Oil Content in Brazilian Genotypes.

Genetic diversity within a germplasm collection plays a vital role in the success of breeding programs. However, comprehending this diversity and identifying accessions with desirable traits pose significant challenges. This study utilized publicly available data to investigate SNP markers associated with protein and oil content in Brazilian soybeans. Through this research, twenty-two new QTLs (Quantitative Trait Loci) were identified, and we highlighted the substantial influence of Roanoke, Lee and Bragg ancestor on the genetic makeup of Brazilian soybean varieties. Our findings demonstrate that certain markers are being lost in modern cultivars, while others maintain or even increase their frequency. These observations indicate genomic regions that have undergone selection during soybean introduction in Brazil and could be valuable in breeding programs aimed at enhancing protein or oil content.

Biological Identification of Skulls in Indonesian and Thai Populations: Ancestry Estimation, Sex Determination, Stature Estimation, and Age Estimation / Identificación Biológica de Cráneos en Poblaciones de Indonesia y Tailandia: Estimación de Ascendencia, Determinación del Sexo, Estimación de Estatura y Estimación de Edad

SUMMARY: This review article will present an overview of biological profiles in forensic utilities. The biological profile of the skull in the existing literature can help to identify humans, especially if the condition of the victim found is a result of mutilation or a bomb explosion. When it comes to the precision of identifying skeletal remains, the human skull is frequently cited as being first in the estimation of age and ancestry and second in terms of sex and stature. It can be an alternative to assessing the following biological parameters: sex, age, stature, and ancestry. The implementation of biological profiles in the identification process is very important considering that some cases require the assistance of forensic anthropology. This review article shows the importance of the value of skulls. The method that can be applied is craniometry which can be used to determine sex, age, stature, and estimated ancestry. Different results will occur depending on the completeness of the skull. Therefore, estimation formulas have different accurate results. Discriminant function analysis has been performed on various measurement sets and its discriminant power has been validated by many researchers. Geometric morphometric analysis has become the main tool for shape analysis and many attempts have been made to use it in analyzing skulls. Several methods supported by technology have also been developed. It is hoped that the review article will show significant differences in results between studies in Thailand and Indonesia, even though they are in the same racial group.

Este artículo presenta una descripción general de los perfiles biológicos en las utilidades forenses. El perfil biológico del cráneo en la literatura existente puede ayudar a identificar a los humanos, especialmente si la condición en la que se encuentra la víctima es el resultado de una mutilación o la explosión de una bomba. Cuando se trata de la precisión en la identificación de restos óseos, el cráneo humano se cita con frecuencia como el primero en la estimación de edad y ascendencia y el segundo en términos de sexo y estatura. Puede ser una alternativa para evaluar los siguientes parámetros biológicos: sexo, edad, estatura y ascendencia. La implementación de perfiles biológicos en el proceso de identificación es importante considerando que algunos casos requieren la asistencia de la antropología forense. Este artículo de revisión muestra la importancia del valor de las cnezas óseas. El método que se puede aplicar es la craneometría para determinar el sexo, la edad, la estatura y la ascendencia estimada. Se pueden obtener diferentes resultados dependiendo de la integridad del cráneo. Por lo tanto, las fórmulas de estimación tienen resultados precisos diferentes. Se ha realizado un análisis de función discriminante en varios conjuntos de medidas y muchos investigadores han validado su poder discriminante. El análisis a través de la morfometría geométrica se ha convertido en la principal herramienta para el análisis de formas y se ha utilizado frecuentemente en el análisis de cráneos. También se han desarrollado varios métodos apoyados en la tecnología. Se espera que este trabajo muestre diferencias significativas en los resultados entre los estudios realizados en Tailandia e Indonesia, aunque pertenezcan al mismo grupo racial.

Many direct-to-consumer canine genetic tests can identify the breed of purebred dogs.

OBJECTIVE: To compare pedigree documentation and genetic test results to evaluate whether user-provided photographs influence the breed ancestry predictions of direct-to-consumer (DTC) genetic tests for dogs. ANIMALS: 12 registered purebred pet dogs representing 12 different breeds. METHODS: Each dog owner submitted 6 buccal swabs, 1 to each of 6 DTC genetic testing companies. Experimenters registered each sample per manufacturer instructions. For half of the dogs, the registration included a photograph of the DNA donor. For the other half of the dogs, photographs were swapped between dogs. DNA analysis and breed ancestry prediction were conducted by each company. The effect of condition (ie, matching vs shuffled photograph) was evaluated for each company's breed predictions. As a positive control, a convolutional neural network was also used to predict breed based solely on the photograph. RESULTS: Results from 5 of the 6 tests always included the dog's registered breed. One test and the convolutional neural network were unlikely to identify the registered breed and frequently returned results that were more similar to the photograph than the DNA. Additionally, differences in the predictions made across all tests underscored the challenge of identifying breed ancestry, even in purebred dogs. CLINICAL RELEVANCE: Veterinarians are likely to encounter patients who have conducted DTC genetic testing and may be asked to explain the results of genetic tests they did not order. This systematic comparison of commercially available tests provides context for interpreting results from consumer-grade DTC genetic testing kits.

Longitudinal follow-up of mixed connective tissue disease and overlapping autoimmune diseases of childhood onset in the Afro-descendant population of the French West Indies.

INTRODUCTION: Overlap autoimmune syndromes (OAS) and mixed connective tissue disease (MCTD) are rare in children. We performed a retrospective, longitudinal and descriptive study of Afro-Caribbean patients from the French West Indies followed for MCTD and OAS to describe their characteristics and outcomes during childhood. METHODS: Retrospective study from January 2000 to 2023. Listings of patients were obtained from multiple sources: computerized hospital archives and national hospital-based surveillance system, registry of pediatricians and adult specialists in internal medicine and the national registry for rare diseases. MCTD was defined according to Kasukawa's criteria. OAS was defined as overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis/autoimmune myositis (DM/AM). RESULTS: Sixteen patients were included over a 23-year period (10 MCTD and 6 OAS). The incidence was 0.23 per 100,000 children-years. The mean age at diagnosis was 11.9 years old (2.4-17) with median follow up of 7.9 years (2.1-19.6). SLE phenotype was present in the highest, followed by SSc and DM/AM. Patients had an average of three flares during childhood (1-7). A quarter (25%) had symptomatic pulmonary arterial hypertension (PAH). Ninety-four percent received steroids during follow-up and 88% required a corticosteroid-sparing therapy. Three patients (19%) developed SLE after more than 10y of follow-up. There were no death and no chronic organ failure. CONCLUSION: This is the largest pediatric cohort of MCTD and OAS in Afro-descendant patients treated in a country with a high standard of care. The clinical evolution did not differ between MCTD and OAS. The main complication was PAH, more frequent in our cohort.

Muscle morphology and architecture of the medial gastrocnemius between typically developing children with different ancestral background.

Muscle ultrasonography is frequently used to improve the understanding of musculoskeletal impairments in children with spastic cerebral palsy (SCP). So far, most studies on muscle morphology and architecture have included typically developing children and children with SCP with similar ancestry, being mainly Caucasian. Less is known about differences in muscle morphology between children with different ancestral backgrounds. Therefore, the aim of this study was to compare muscle morphology and architecture of the medial gastrocnemius in typically developing children with African, South Asian and Southeast Asian descent from Suriname. This explorative cohort study identified children as Maroon (Ghana, African descent), Hindustani (India, South Asian) or Javanese (Indonesia, Southeast Asian), aged 5-10 years. Using 3D freehand ultrasound with the subject prone, the following medial gastrocnemius parameters were defined: muscle tendon unit (MTU) length, muscle belly length, tendon length, muscle volume, muscle thickness, anatomical cross-sectional area (ACSA), fascicle length, pennation angle, and physiological cross-sectional area (PCSA). In addition, differences between ancestral groups were assessed for the length of the MTU, muscle, tendon and fascicles in two passive stretch conditions corresponding to an externally applied joint torque of 1Nm and 4Nm. One-way ANOVA with post hoc t-tests were used to investigate differences between the ancestral groups. In total, 100 Hindustani (n = 34), Javanese (n = 34) and Maroon (n = 32) children were included. For statistical analyses, we matched the children by age, which resulted in groups of 25 children per ancestral group (n = 75). There were no differences found in MTU length, muscle belly length, ACSA, PCSA and muscle volume. Tendon length, fascicle length and pennation angle were different between ancestral groups. Compared to Javanese children, tendon length was longer (p = 0.001) and pennation angle (p = 0.001) was larger in Maroon children and fascicle length was shorter in both Maroon and Hindustani children (p < 0.001). While there was a difference found in MTU length at different conditions of passive stretch between ancestries, no differences were found in the muscle, tendon and fascicles. This is the first study that investigated macroscopic morphological and architectural parameters for the medial gastrocnemius in one extended cohort of typically developing children, stratified in three ancestral subgroups. The current results imply that ancestry-specific reference data for children are needed, especially for tendon length, fascicle length and pennation angle when investigating altered muscle morphology in neurological or neuromuscular pathologies, such as SCP. Future studies should report the ancestral background when describing muscle morphology and architecture of children and ancestral specifications should be included in normative databases.