First Report of Mexican Patients with PACS1-Related Neurodevelopmental Disorder and Review of the PACS1-, PACS2-, and WDR37-Related Ophthalmological Manifestations.

Introduction: PACS1-related neurodevelopmental disorder (PACS1-related NDD) is caused by pathogenic variants in the PACS1 gene and is characterized by a distinctive facial appearance, intellectual disability, speech delay, seizures, feeding difficulties, cryptorchidism, hernias, and structural anomalies of the brain, heart, eye, and kidney. There is a marked facial resemblance and a common multisystem affectation with patients carrying pathogenic variants in the WDR37 and PACS2 genes, although they vary in terms of severity and eye involvement. Case Presentation: Here, we describe 4 individuals with PACS1-related NDD from Mexico, all of them carrying a de novo PACS1 variant c.607C>T; p.(Arg203Trp) identified by exome sequencing. In addition to eye colobomata, this report identified corneal leukoma, cataracts, and tortuosity of retinal vessels as ophthalmic manifestations not previously reported in patients with PACS1-related NDD. Discussion: We reviewed the ocular phenotypes reported in 74 individuals with PACS1-related NDD and the overlaps with WDR37- and PACS2-related syndromes. We found that the 3 syndromes have in common the presence of colobomata, ptosis, nystagmus, strabismus, and refractive errors, whereas microphthalmia, microcornea, and Peters anomaly are found only among individuals with PACS1-related NDD and WDR37 syndrome, being more severe in the latter. This supports the previous statement that the so-called WDR37-PACS1-PACS2 axis might have an important role in ocular development and also that the specific ocular findings could be useful in the clinical differentiation between these related syndromes.

[Genetic aspects involved in asthma]. / Aspectos genéticos implicados en el asma.

Asthma is an etiologically heterogeneous disease resulting from a complex interaction between genetic. The genetic aspects involved in asthma, which were analyzed from the perspective of the traditional model of multifactorial inheritance, were susceptibility, host factors, and environmental exposures. In the present paper, studies on their family aggregation, concordance in twins, and heritability were analized; as well as the current knowledge about candidate genes, genome wide association studies, and epigenomics contributions and other omic studies that have increased our knowledge about their pathophysiology and environmental interactions.

El asma es una patología etiológicamente heterogénea resultante de una compleja interacción entre una susceptibilidad genética, factores del huésped y exposiciones ambientales. En el presente trabajo se revisan los aspectos genéticos implicados en el asma, los cuales fueron analizados desde la perspectiva del modelo tradicional de la herencia multifactorial. Fueron incluidos los estudios sobre su agregación familiar, concordancia en gemelos y heredabilidad, así como el conocimiento actual sobre genes candidatos, estudios de asociación amplia del genoma y las recientes contribuciones de la epigenómica y otros estudios ómicos, que en conjunto han aumentado nuestro conocimiento sobre su fisiopatología e interacciones ambientales.

Prevalence of open neural tube defects and risk factors related to isolated anencephaly and spina bifida in live births from the "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara (Jalisco, Mexico).

We determine the prevalence and trends of open neural tube defects (ONTDs) during 1991 to 2019 at the "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara (Mexico). Also, details of potential risks were obtained in 662 newborns, including those 143 patients with anencephaly and open spina bifida (OSB) classified as isolated (cases) and 519 controls. Data were analyzed using multivariable logistic regression. Among 267 201 live births during the study period, 336 were born with ONTDs, yielding an overall prevalence of 12.6 per 10 000. After folic acid (FA)-related programs began in Mexico (2003-2019), only OSB showed a decline of 20.6%. For anencephaly, associated risks included relatives with neural tube defects (NTDs) (adjusted odds ratio [aOR]: 67.9, 95% confidence interval [95% CI]: 11.3-409.8), pre-pregnancy body mass index (BMI) ≥25 kg/m2 (aOR: 2.6, 95% CI: 1.1-6.0), insufficient gestational weight gain (aOR: 3.0, 95% CI: 1.3-7.1), parity ≥4 (aOR: 3.2, 95% CI: 1.3-7.7), and exposure to analgesic/antipyretic drugs (aOR: 9.0; 95% CI: 2.5-33.0). For OSB, associated risks included consanguinity (aOR: 14.0, 95% CI: 3.5-55.9), relatives with NTDs (aOR: 22.4, 95% CI: 4.5-112.9), BMI ≥25 kg/m2 (aOR: 2.5, 95% CI: 1.6-4.2), insufficient gestational weight gain (aOR: 1.9, 95% CI: 1.1-3.1), and exposures to hyperthermia (aOR: 2.3, 95% CI: 1.2-4.3), common cold (aOR: 6.8, 95% CI: 3.6-12.7), and analgesic/antipyretic drugs (aOR: 3.6, 95% CI: 1.3-10.0). Our high rate probably results from exposures to preventable risks, most related to FA, indicating a need for strengthening existing FA-related programs in Mexico.