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BACKGROUND: LIPA, situated on chromosome 10q23.2-q23.3, encodes the enzyme lysosomal acid lipase (LAL) (EC 3.1.1.13). Genetic alterations in LIPA lead to lysosomal acid lipase deficiency (LALD), an inborn error causing lipid metabolism anomalies and impairing cholesterol and triacylglyceride degradation. Over 40 LIPA variants have been documented, yet this study focuses on just two. The rs1051338 variant (NM_000235:c.46A>C) affects the signal peptide in Exon 2, whereas rs116928232, located in Exon 8, alters the splice site (NM_000235:c.894G>A), impacting lysosomal acid lipase activity. Considering the diverse clinical manifestations of LALD and the rising hepatic steatosis prevalence in Mexican population, mainly due to diet, these variants were investigated within this demographic to uncover potential contributing factors. This study aimed to reveal the frequency of rs1051338 and rs116928232 among healthy mestizo individuals in Northwest Mexico, marking a significant genetic exploration in this demographic. METHODS: Three hundred ten healthy mestizo individuals underwent PCR-RFLP analysis for both variants, and Sanger sequencing was performed for variant rs116928232. Bioinformatic analysis was also performed to predict protein changes. RESULTS: Allele frequencies for rs1051338 (FA = 0.39, p value = 0.15) and rs116928232 (FA = 0.0016, p value = 0.49) aligned with reported data, while bioinformatic analysis allowed us to identify the protein alteration observed in both variants; finally, the variants showed no linkage between them (normalized D' = 1.03, p value = 0.56). CONCLUSIONS: Allelic frequencies closely matched reported data, and protein structure analysis confirmed variant impacts on LAL enzyme function. Notably, this study marks the first analysis of rs1051338 and rs116928232 in a healthy Mexican mestizo population.

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The Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF) studies Latin American populations to benefit from the implementation of personalized medicine. Since 2006, it has studied ethnicity to apply pharmacogenetics knowledge in autochthonous populations of Latin America, considering ancestral medicine. The meeting 'Pharmacogenetics: ethnicity, Treatment and Health in Latin American Populations' was held in Mexico City, Mexico, and presented the relevance of RIBEF collaboration with Latin American researchers and the governments of Mexico, Spain and the Autonomous Community of Extremadura. The results of 17 years of uninterrupted work by RIBEF, the Declaration of Mérida/T'Hó and the call for the Dr José María Cantú Award for studies focused on the pharmacogenetics of native populations in Latin America were presented.

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Resumen OBJETIVO: Identificar las causas de hidrops fetal no inmunitario en un hospital obstétrico de referencia del Occidente de México. MATERIALES Y MÉTODOS: Estudio de serie de casos, con un muestreo no probabilístico por conveniencia, llevado a cabo de octubre de 2014 a septiembre de 2015 al que se incluyeron pacientes (entre las 15 y 38 semanas de embarazo), mayores de edad (en casos de menores de edad se solicitó consentimiento informado a los padres o tutores), con diagnóstico de hidrops fetal por ultrasonido obstétrico. Para el análisis estadístico se generó una base de datos en Excel y se aplicó estadística descriptiva. RESULTADOS: Se reunieron 33 embarazadas en quienes el hidrops fetal no inmunitario fue el más frecuente (n = 31) y la causa idiopática más común (n = 10) seguida por errores innatos del metabolismo, alteraciones cromosómicas y cardiacas (n = 6 de cada una). Posteriormente, las causas hematológicas (n = 4), linfáticas y sindrómicas (n = 3 de cada una), y las infecciosas y tumorales (n = 1 de cada una). En este estudio los errores innatos del metabolismo (específicamente síndrome Sly) tuvieron una frecuencia superior a la referida en la bibliografía. CONCLUSIONES: Los errores innatos del metabolismo, las anomalías cromosómicas y cardiacas fueron la segunda causa más frecuente de hidrops fetal no inmunitario. Se sugiere tener en cuenta las causas metabólicas en el enfoque diagnóstico del hidrops fetal, sobre todo para el establecimiento del tratamiento temprano.

Abstract OBJECTIVE: To identify the causes of nonimmune fetal hydrops fetalis in an obstetric referral hospital in Western Mexico. MATERIALS AND METHODS: Case series study, with non-probabilistic sampling by convenience, carried out from October 2014 to September 2015 which included patients (between 15 and 38 weeks of pregnancy), of legal age (in cases of minors, informed consent was requested from parents or guardians), with a diagnosis of fetal hydrops fetalis by obstetric ultrasound. For statistical analysis, an Excel database was generated and descriptive statistics were applied. RESULTS: Thirty-three pregnant women were included, in whom non-immune fetal hydrops fetalis was the most frequent (94%) and idiopathic was the most common cause (n = 10), followed by inborn errors of metabolism, chromosomal and cardiac alterations (n = 6 each). This was followed by hematologic (n = 4), lymphatic and syndromic causes (n = 3 each), and infectious and tumor causes (n = 1 each). In this study, inborn errors of metabolism (specifically Sly syndrome) had a higher frequency than that reported in the literature. CONCLUSIONS: Inborn errors of metabolism, chromosomal and cardiac abnormalities were the second most frequent cause of nonimmune fetal hydrops. It is suggested that metabolic causes be taken into account in the diagnostic approach to fetal hydrops, especially for the establishment of early treatment.

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Sialidosis is a rare autosomal recessive disease that presents with progressive lysosomal storage of sialylated glycopeptides and oligosaccharides caused by homozygous or compound heterozygous sequence variants in the neuraminidase 1 (NEU1) gene. These sequence variants can lead to sialidosis type I and II; the latter is the most severe and presents prenatally or at early age. However, sialidosis diagnosis is challenging, especially in those health systems with limited resources of developing countries. Consequently, it is necessary to dip into high-throughput molecular diagnostic tools to allow for an accurate diagnosis with better cost-effectiveness and turnaround time. We report a 4-member pedigree segregating an ultrarare missense variant, c.1109A>G; p.Tyr370Cys, in NEU1 as detected by whole-exome sequencing. Two short-lived siblings, who presented with previously unreported clinical features from such a homozygous sequence variant, were diagnosed with sialidosis type II. Additionally, we present a novel molecular model exhibiting the consequences of the variant in the sialidase-1 tridimensional structure. This study allowed us to provide a definitive diagnosis for our patients, increase our understanding of this pathogenic variant, and improve genetic counseling.

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The spinocerebellar ataxia type 2 is a neurodegenerative disease with autosomal dominant inheritance; clinically characterized by progressive cerebellar ataxia, slow ocular saccades, nystagmus, ophthalmoplegia, dysarthria, dysphagia, cognitive deterioration, mild dementia, peripheral neuropathy. Infantile onset is a rare presentation that only has been reported in four instances in the literature. In the present work a boy aged 5 years 7 months was studied due to horizontal gaze-evoked nystagmus, without saccades, ataxic gait, dysarthria, dysphagia, dysmetria, generalized spasticity mainly pelvic, bilateral Babinsky. The mother aged 27 years-old presented progressive cerebellar ataxia, dysarthria, dysmetria, dysdiadochokinesis, limb ataxia and olivopontocerebellar atrophy. The molecular analysis was made by identifying the expansion repeats in tandem by long PCR to analyze the repeats in the ATXN2 gene. We found an extreme CAG expansion repeats of ~884 repeats in the child. We describe a Mexican child affected by SCA2 with an infantile onset, associated with a high number of CAG repeats previously no reported and anticipation phenomenon.

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Mucopolysaccharidoses (MPS) are a group of genetic disorders, each resulting from the deficiency of one of the lysosomal enzymes that catabolizes mucopolysaccharides. For the accurate diagnosis of the disease, the quantification of a specific enzymatic activity is needed. In the present study, we analyzed seven MPS over several periods of time ranging from 2 to 5 years in a reference center in Mexico. During this time, a total of 761 samples belonging to 505 individuals with suspected MPS were analyzed. A total of 198 (26.01%) positive results were found. Among these, MPS IVA accounted for the highest frequency of positive results (49.10%), followed by MPS III (17.69%, IIIA: 11.80% and IIIB: 5.89%). Adjusting for the number of births per year, the estimated incidence per 100,000 births for MPS analyzed were as follows: MPS I: 0.19, MPS II: 0.15, MPS IIIA: 0.26, MPS IIIB: 0.13, MPS IVA: 1.10, MPS VI: 0.17 and MPS VII: 0.23, and the combined estimated incidence of MPS was 2.23 per 100,000 births; however, this incidence seems to be highly underestimated when compared with the results of newborn screenings.

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Williams-Beuren syndrome (WBS) has a prevalence of 1/7500-20000 live births and results principally from a de novo deletion in 7q11.23 with a length of 1.5 Mb or 1.8 Mb. This study aimed to determine the frequency of 7q11.23 deletion, size of the segment lost, and involved genes in 47 patients with a clinical diagnosis of WBS and analysed by fluorescence in situ hybridization (FISH); among them, 31 had the expected deletion. Micro-array comparative genomic hybridization (aCGH) confirmed the loss in all 18 positive-patients tested: 14 patients had a 1.5 Mb deletion with the same breakpoints at 7q11.23 (hg19: 72726578-74139390) and comprising 24 coding genes from TRIM50 to GTF2I. Four patients showed an atypical deletion: two had a 1.6 Mb loss encompassing 27 coding genes, from NSUN5 to GTF2IRD2; another had a 1.7 Mb deletion involving 27 coding genes, from POM121 to GTF2I; the remaining patient presented a deletion of 1.2 Mb that included 21 coding genes from POM121 to LIMK1. aCGH confirmed the lack of deletion in 5/16 negative-patients by FISH. All 47 patients had the characteristic facial phenotype of WBS and 45 of 47 had the typical behavioural and developmental abnormalities. Our observations further confirm that patients with a classical deletion present a typical WBS phenotype, whereas those with a high (criteria of the American Association of Pediatrics, APP) clinical score but lacking the expected deletion may harbour an ELN point mutation. Overall, the concomitant CNVs appeared to be incidental findings.

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BACKGROUND: Disruptive amniotic band sequence (DABS) is a sporadic, non-familial disorder with unclear etiology. Diagnosis is based on clinical features because there is currently no reliable laboratory diagnostic tests. OBJECTIVE: We describe six cases of DABS with severe craniofacial deformations, three with and three without classical constrictive limb deformation. RESULTS: The craniofacial deformities were delimited by peripheral sharply demarcated scarring. CONCLUSION: When a sharply demarcated linear disruptive craniofacial lesion is observed, DABS should be considered despite the absence of constrictive limb scarring.

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The original version of this article unfortunately contained two mistakes in the Abstract and the Discussion sections that the authors would like to correct.

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Preeclampsia is a condition associated with high rates of maternal-fetal morbidity and mortality. It usually occurs in 3-10% of nulliparous women and 18% of previously affected women. Different lines of evidence have demonstrated the role of the father in the onset of preeclampsia. The placenta is the cornerstone of preeclampsia and poses important paternal genetic determinants; in fact, the existence of a "paternal antigen" has been proposed. Nulliparity is a well-known risk factor. Change of partner to a woman without history of preeclampsia increases the risk; however, this change decreases in women with history of the condition. High interval between pregnancies, short sexual intercourse before pregnancy, and conception by intracytoplasmic sperm injection suggest a limited exposure to the so-called paternal antigen. A man who was born from a mother with preeclampsia also increases the risk to his partner. Not only maternal but also paternal obesity is a risk factor for preeclampsia. Fetal HLA-G variants from the father increased the immune incompatibility with the mother and are also significantly associated with preeclampsia in multigravida pregnancies. An analysis of a group of Swedish pregnant women showed that the risk for preeclampsia is attributable to paternal factors in 13% of cases, which could be related to genetic interactions with maternal genetic factors. This review aimed to evaluate the evidences of the father's contribution to the onset of preeclampsia and determine the importance of including them in future studies.

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INTRODUCTION: Recurrent spontaneous abortion (RSA) is a multifactorial condition that occurs with a frequency of 0.2-5% in women of reproductive age. Among genetic factors, the single nucleotide polymorphism (SNP) G1733A in the androgen receptor (AR) gene has been associated with its presence in Greek and Iranian populations. Therefore, the aim of this study is to determine its possible association with RSA in this population. PATIENTS AND METHODS: A total of 156 Mexican RSA (with at least 2 consecutive abortions) unrelated patients and 152 unrelated healthy women were included, the presence of karyotype anomalies in the parents as well as uterine anomalies as well as antiphospholipid antibodies was excluded in patients; while all the controls presented at least two healthy pregnancies and no abortion. In all the included women, the presence of the SNP G1733A was determined by restriction fragment length polymorphism (RFLP) technique. RESULTS: No significant differences were observed in age between groups. The genotype GG, GA, and AA had a frequency of 0.70, 0.27, and 0.03 in patients and of 0.89, 0.10, and 0.01 in controls [corrected] (p < 0.001); while the A allele frequency was of 0.06 and 0.16 in controls and patients, respectively (p < 0.0001). The difference in allele frequency increased 10-15% when patients with primary RSA (with no live births) and with at least three abortions were included. CONCLUSIONS: The SNP G1733A of the AR gene is significantly associated with RSA in Mexican patients. These results coincide with previous reports in other populations.

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Chitotriosidase (CHIT, EC 3.2.1.14) is an enzyme secreted by activated macrophages with the ability to hydrolyze the chitin of pathogens. The high activity of this enzyme has been used as a secondary biomarker of response to treatment in patients with Gaucher disease (OMIM 230800). Within the world's population, approximately 6% is homozygous and 35% is heterozygous for the most common polymorphism in the CHIT1 gene, a 24-bp duplication (dup-24 bp), with homozygosity of this duplication causing inactivation of the enzyme but without major consequences for health. To determine the frequency of the dup-24 bp CHIT1 gene in indigenous populations from Mexico, 692 samples were analyzed: Purepecha (49), Tarahumara (97), Huichol (97), Mayan (139), Tenek (97), and Nahua (213). We found that the groups were in Hardy-Weinberg equilibrium. The dup-24 bp allele frequency was found to be (in order of highest to lowest) 37% (Mayan), 34% (Huichol and Nahua), 33% (Purepecha), 31% (Tenek), and 29% (Tarahumara).

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Human leukocyte antigen is a class I HLA classic molecule that is preferentially expressed in cytotrophoblast cells and participates in tolerance and immune system suppression. The expression of HLA-G is induced in viral infections, autoimmune disorders, and cancers. Currently, HLA-G is considered a biomarker in the diagnosis, prognosis, and therapy of cancer.

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BACKGROUND: human chitotriosidase is a secreted enzyme by activated macrophages, detectable in plasma. Levels of chitotriosidase indicate severity of Gaucher disease and monitoring the efficiency of the enzyme replacement therapy. The most frequent polymorphism in chitotriosidase-1 gene (CHIT1) corresponds to a 24-bp duplication (24-bp Dup) that in homozygotes individuals gives place to the enzyme inactivation. The objective was to identify in a sample of Mexican health population the 24-bp Dup in CHIT1 gene and determinate the allelic and genotypic frequencies. METHODS: 306 DNA samples of healthy individuals were analyzed in polyacrylamide gels and the allelic and genotypic frequencies was determined with SPSS v. 13.0. RESULTS: distribution of the 24-bp Dup was in accordance to Hardy-Weinberg equilibrium (p = 0.90), with an allelic frequency of 23.86 %. Genotypic frequencies for homozygous and hetero-zygotes were of 5.56 % and 36.60 % respectively. CONCLUSIONS: allelic and genotypic frequencies of the 24-bp Dup in CHIT1 gene in homozygotes and heterozygotes were in accordance to worldwide reports.

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PURPOSE: The frequency of primary congenital glaucoma (PCG)-causing CYP1B1 mutations varies importantly among distinct populations, ranging from 20% in Indonesians and Japanese to about 100% among the Saudi Arabians and Slovakian Gypsies. Thus, the molecular characterization of large groups of PCG from different ethnic backgrounds is important to establish the actual CYP1B1 contribution in specific populations. In this work, the molecular analysis of the CYP1B1 gene in a group of Mexican PCG patients is reported. MATERIAL AND METHODS: Thirty unrelated Mexican patients fulfilling the clinical criteria for PCG were included. Two cases were familial and with proven consanguinity, originating from distinct regions of the country. Polymerase chain reaction amplification and direct automated sequencing of the CYP1B1 coding region was performed in each participating subject. RESULTS: An identical pathogenic CYP1B1 mutation was demonstrated in 2 unrelated PCG subjects. The mutation consisted of a homozygous G to A transition at nucleotide position 1505 in exon 3, which predicted a substitution of glutamic acid for lysine at residue 387 of the protein (E387K). In the remaining 28 PCG subjects, no deleterious mutations were identified. Both subjects with the E387K mutation shared a same haplotype for 5 CYP1B1 intragenic single nucleotide polymorphisms, indicating a common origin of the allele. CONCLUSIONS: Mexican patients with PCG are rarely (less than 10%) due to CYP1B1 mutations. Available data indicate that most of the non-Brazilian Latin American PCG patients investigated to date are not due to CYP1B1 defects. Populations with low incidence of CYP1B1 mutations are appropriate candidates for the identification of novel PCG-causing genes.

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