MTHFR 677C>T and 1298A>C Variants in Mothers of Infants with Down Syndrome from Western Mexico.

Background: Several studies in mothers of infants with Down syndrome (DS) (MoIDS) have suggested that the 677C>T and 1298A>C variants of the 5,10-methylentetrahydrofolate reductase (MTHFR) gene can increase the risk of having a child with DS. Aim: This study aimed to evaluate the MTHFR 677C>T and 1298A>C variants as potential maternal risk factors for DS. Materials and Methods: Using TaqMan allelic discrimination assay, we genotyped 95 MoIDS and 164 control mothers from western Mexico. Data were analyzed using logistic regression analysis. Results: We found that MoIDS had a significantly higher risk for the MTHFR 677TT genotype (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.1-10.6), and the MTHFR 677T allele (aOR = 1.5, 95% CI: 1.0-2.3), particularly in MoIDS <35 years of age. Conclusions: Our findings indicate that the presence of the 677TT genotype and 677T allele of the MTHFR 677C>T variant are maternal risk factors for DS in Mexican MoIDS.

Complete blood count differences in a cohort of Down syndrome neonates with transient abnormal myelopoiesis screened for GATA1 pathogenic variants.

Transient abnormal myelopoiesis (TAM) raises the risk for acute myeloid leukemia of Down syndrome (DS) (ML-DS), and both are related to GATA1 pathogenic variants. Here, we analyzed which findings on complete blood count (CBC) are associated with TAM in a cohort of neonates with DS screened for GATA1 pathogenic variants. The CBCs were compared among 70 newborns with DS, including 16 patients (22.9%) with TAM (cases), and 54 patients (77.1%) without TAM (controls). TAM was defined as peripheral circulating blasts (PCBs) ≥ 1%. PCR and direct sequencing were used to screen DNA samples from peripheral blood for GATA1 exon 2 mutations. Multivariate logistic regression analyses determined that the mean count of lymphocytes was significantly higher in DS infants with TAM (p = .035) and that lymphocytosis confers a risk for TAM (adjusted odds ratio = 7.23, 95% confidence intervals: 2.02-25.92). Pathogenic variants of GATA1 were identified in 2 of 70 analyzed DS neonates (2.9%), of which one had ML-DS and another had an asymptomatic TAM. Among those DS infants with TAM, the GATA1 pathogenic variant detection was 12.5%. Our results indicated that lymphocytosis is associated with TAM in neonates with DS. However, since not all infants with an abnormal CBC had TAM, and not all infants with TAM had GATA1 pathogenic variants, we emphasize that only the search for GATA1 pathogenic variants allows the proper identification of the subgroup of DS infants with a real increasing in risk for ML-DS.

Prevalence and risk factors for Down syndrome: A hospital-based single-center study in Western Mexico.

Although Hispanics of Mexican origin in the United States have been identified as a population with a particularly higher rate of Down syndrome (DS), there is a paucity of studies concerning this topic in Mexico. The aim of this study was to determine the prevalence and risk factors for DS in a population from Western Mexico. For prevalence, 230 liveborn infants with DS were included from a total of 89,332 births occurring during the period 2009-2017 at the Dr. Juan I. Menchaca Civil Hospital of Guadalajara (Mexico). In order to evaluate potential DS risks, a case-control study was conducted among 633 newborns, including those 211 DS patients with full trisomy 21 (cases) and 422 infants without birth defects (controls). Data were analyzed using multivariable logistic regression analysis. The overall prevalence for DS was 25.7 per 10,000 (95% confidence interval [95% CI]: 22.4-29.1). Patients with DS had a significantly higher risk for family history of DS in distant relatives (adjusted odds ratio [aOR] = 4.4, 95% CI: 2.5-7.7), relatives with thyroid disease (aOR = 2.3, 95% CI: 1.2-4.0), maternal age ≤ 19 years (aOR = 5.1, 95% CI: 2.7-9.6) or ≥ 35 years (aOR = 3.3, 95% CI: 1.5-6.9), paternal age ≤ 19 years (aOR = 3.5, 95% CI: 1.7-7.4), pre-pregnancy BMI ≥ 25 kg/m2 (aOR = 1.6, 95% CI: 1.0-2.4), and pre-pregnancy alcohol consumption (aOR = 1.8, 95% CI: 1.1-2.9). The identified risks in family history, and previously mentioned nutritional disadvantages were associated with DS in our sample and probably also to its increased prevalence in our population.

Ring chromosome 6 in a child with anterior segment dysgenesis and review of its overlap with other FOXC1 deletion phenotypes.

Here, we report a patient with ring chromosome 6 [r(6)], associated with anterior segment dysgenesis (ASD) and other anomalies. The phenotype was due to a 1880 kb microdeletion at 6p25.3 identified by whole-genome array analysis, and was mainly attributable to a FOXC1 haploinsufficiency. Currently 37 patients with r(6) have been reported. We found that facial dysmorphism, ASD, heart anomalies, brain anomalies, and hearing loss are constant features only in severe cases of r(6), mainly related to hemizygosity of FOXC1. Thus, overlaps with other FOXC1 related phenotypes, such as the 6p25 deletion syndrome, Axenfeld-Rieger syndrome type 3, and ASD type 3. Contrarily, those patients whose r(6) does not disrupt FOXC1, have mild or moderate phenotypes and do not exhibit ASD.