Familial LCAT Deficiency and Low HDL-C Levels: In silico Characterization of Two Rare LCAT Missense Mutations.

Mutations in the lecithin-cholesterol acyltransferase (LCAT) gene, which catalyzes the esterification of cholesterol, result in two types of autosomal recessive disorders: Familial LCAT deficiency (FLD) and Fish Eye Disease (FED). While both phenotypes are characterized by corneal opacities and different forms of dyslipidemia, such as low levels of high-density lipoprotein-cholesterol (HDL-C), FLD exhibits more severe clinical manifestations like splenomegaly, anemia, and renal failure. We describe the first clinically and genetically confirmed case of FLD in Colombia which corresponds to a 46-year-old woman with corneal opacity, hypothyroidism, and dyslipidemia, who does not have any manifestations of renal failure, with two pathogenic heterozygous missense variants in the LCAT gene: LCAT (NM_000229.2):c.803G>A (p.Arg268His) and LCAT (NM_000229.2):c.368G>C (p.Arg123Pro). In silico analysis of the mutations predicted the physicochemical properties of the mutated protein, causing instability and potentially decreased LCAT function. These compound mutations highlight the clinical heterogeneity of the phenotypes associated with LCAT gene mutations.

Novel mutation in RPGRIP1L gene causing Joubert syndrome: A case report.

INTRODUCTION: Joubert syndrome is a rare disease of genetic origin with autosomal recessive inheritance and extreme genetic heterogeneity with more than 40 causative genes. Joubert syndrome 7 is caused by mutations in the RPGRIP1L gene. PATIENT CONCERNS: Our report describes a pediatric patient with clinical features compatible with JS type 7 such as hypotonia, developmental delay and aplasia of the cerebellar vermis. DIAGNOSIS: The clinical features and the MRI of the head and neck which showed alterations at the level of the posterior fossa, with absence of the vermis and horizontal disposition of the cerebellar peduncles, were compatible with Joubert syndrome. Whole exome sequencing detected the variants RPGRIP1L (NM_015272.2) c.697A > T (p. Lys233Ter) and RPGRIP1L (NM_015272.2) c.3545 del (p.Pro1182LeufsTer25). INTERVENTIONS: Resection was performed to correct the polydactyly. At age 2 years umbilical hernia, adenoid surgery and ventilatory tubes surgery were performed. Renal biopsy confirmed interstitial fibrosis and focally accentuated mild tubular atrophy with focal tubular hypertrophy, compatible with the clinical suspicion of Joubert syndrome. Congenital hip dislocation surgery was performed. The patient underwent surgery for correction of concomitant divergent strabismus and continued with glasses for astigmatism and hyperopia. OUTCOMES: Sanger sequencing confirmed the patient´s results and the father was found to be a carrier of RPGRIP1L (NM_015272.2) c.697A > T (p. Lys233Ter) and the mother and maternal grandmother as carriers of RPGRIP1L (NM_015272.2) c.3545del (p.Pro1182LeufsTer25). RPGRIP1L:c.3545del novel variant is a deletion which changes the reading frame, altering the RPGR1_C terminal domain and giving rise to an incomplete protein whose functions will be altered. CONCLUSION: This is the first genetically confirmed case of JS in Colombia, the first carrier of biallelic RPGRIP1L gene mutations with hip dislocation and incomplete glottic closure and the first report of the novel c.3545del likely pathogenic variant causing JS.

Case report: Novel frameshift mutation in LAMA2 gene causing congenital muscular dystrophy type 1A.

Congenital muscular dystrophy type 1A (CMD1A) is a rare autosomal recessive disorder caused by mutations in the LAMA2 gene. CMD1A is characterized by peripheral hypotonia and muscle weakness from the first months of life, cerebral white matter abnormalities, and elevated creatine phosphokinase (CPK) levels. We describe an 8-year-old girl from Colombia with clinical features compatible with CMD1A, severe scoliosis corrected with surgery, and feeding difficulty corrected with a gastrostomy. Whole-exome sequencing identified two heterozygous variants: a reported nonsense variant (LAMA2 NM_000426.3:c.4198C>T) and a novel likely pathogenic variant (LAMA2 NM_000426.3:c.9227_9243dup). This is the first genetically confirmed case of CMD1A in Colombia and the first report of the c.9227_9243dup variant causing CMD1A.

Frequency of polymorphisms in the CYP2C9, VKORC1, and CYP4F2 genes related to the metabolism of Warfarin in healthy donors from Cali, Colombia.

Alleles in the VKORC1, CYP2C9, and CYP4F2 genes can influence Warfarin dose requirement. We aimed to determine the frequency of the polymorphisms in these genes in healthy individuals from Cali, Colombia. Observational study where total blood was collected from 107 healthy donors who attended a higher educational institution in Cali, Colombia. Sanger sequencing of exons 2, 3, 5, and 7 of the CYP2C9 gene; the common promoter region of CYP (rs12777823); exon 11 of CPY4F2 and the polymorphism c.-1639G > A in the VKORC1 gene promoter was performed. CYP2C9*2, CYP2C9*3, CYP2C9*8, CYP2C9*9, CYP2C9*11, CYP4F2*3, rs12777823, and VKORC1*2 were detected. The latter had the highest frequency with 80 (74.8%) participants in a heterozygous or homozygous state. The least frequent allele was CYP2C9*11 with only 1 carrier. Combined haplotypes (VKORC1 *1/*2 or *2/*2 and CYP2C9 *1/*2 or *2/*2) were identified in 14 (13.7%) subjects. Both frequencies found in the VKORC1 and CYP2C9 alleles were similar to the ones reported for Latin Americans of European and Native American Ancestry. VKORC1*2 allele, the main genetic contributor to Warfarin dosing requirement, was the variant with the highest frequency (74.8% subjects, with a frequency of the alternative allele (A) of 50%). Our findings provide researchers with a greater insight regarding the frequency of common polymorphisms that affect anticoagulation treatment in the Cali (Colombia) population.

Detección molecular de Toxoplasma gondii en carnes para consumo humano en Ibagué, Colombia / Molecular detection of Toxoplasma gondii in meat for human consumption in Ibague, Colombia

Introducción. Toxoplasma gondii es un parásito con gran potencial zoonótico que puede infectar un amplio rango de huéspedes de sangre caliente, incluidos los animales del sector pecuario, lo que causa pérdidas a la industria. En el humano, es patógeno en personas inmunosuprimidas y afecta el desarrollo del feto en infecciones congénitas. Además, se asocia con diversos trastornos del comportamiento en personas sanas. El humano puede adquirir T. gondii al consumir carnes contaminadas mal cocidas. Objetivo. Determinar la positividad de T. gondii en carnes de consumo humano (res, pollo y cerdo) en Ibagué, Colombia. Materiales y métodos. Se utilizó la PCR convencional anidada y la secuencia del gen B1 de T. gondii como blanco de amplificación. Se tomaron 186 muestras de carne comercializada en la zona urbana de Ibagué (62 de res, 62 de pollo y 62 de cerdo) y se obtuvo el porcentaje de positividad en cada tipo de carne evaluada. Resultados. Se encontró un porcentaje de positividad de 18,8 % en las muestras, siendo la carne de cerdo la del mayor porcentaje (22,5 %; 14/62), seguida por las muestras de carne de res (19,3 %; 12/62) y de pollo (14,5 %; 9/62). Los mejores productos amplificados fueron secuenciados en Macrogen, y alineados con las secuencias del gen B1 depositadas en el GenBank, con lo que se confirmó su identidad. Conclusiones. Este es el primer estudio sobre prevalencia de T. gondii en carnes para consumo humano en Ibagué y el departamento del Tolima. Se demostró que los tres tipos de carne representan un riesgo para la infección en humanos a nivel local.

Introduction: Toxoplasma gondii is a parasite with great zoonotic potential. It can infect a broad range of warm-blooded hosts (including livestock) and causes significant losses in the industry. In humans, it has been described as a pathogen in immunosuppressed people, it affects the fetus development in congenital infections, and is associated with various behavioral disorders in healthy people. Humans can acquire T. gondii by consuming undercooked, contaminated meat. Objective: To determine T. gondii positivity (currently unknown) in meat for human consumption (i.e., beef, chicken, and pork) in the city of Ibague, Colombia. Materials and methods: We used conventional nested PCR and the T. gondii B1 gene sequence as amplification target. We collected samples of meat (N=186) sold in the urban area of Ibagué (62 beef, 62 chicken, and 62 pork samples) and determined the T. gondii positivity percentage for each type of meat. Results: The study found an average of 18.8% positivity for all meat samples, pork having the highest percentage (22.5%; 14/62), followed by beef (19.3%; 12/62) and chicken (14.5%; 9/62). The best-amplified products were sequenced by macrogen and aligned with the B1 gene sequences in GenBank, thereby confirming their identity. Conclusions: This is the first study of T. gondii prevalence in meat for human consumption carried out in the city of Ibagué and the department of Tolima. All three types of meat sampled represent a risk for local human infection.

Physico-chemical and biological treatment strategies for converting municipal wastewater and its residue to resources.

An increase in urbanization and industrialization has not only contributed to an improvement in the lifestyle of people, but it has also contributed to a surge in the generation of wastewater. To date, conventional physico-chemical and biological treatment methods are widely used for the treatment of wastewater. However, the efficient operation of these systems require substantial operation and maintenance costs, and the application of novel technologies for the treatment and disposal of sludge/residues. This review paper focuses on the application of different treatment options such as chemical, catalyst-based, thermochemical and biological processes for wastewater or sludge treatment and membrane-based technologies (i.e. pressure-driven and non-pressure driven) for the separation of the recovered products from wastewater and its residues. As evident from the literature, a wide variety of treatment and resource recovery options are possible, both from wastewater and its residues; however, the lack of planning and selecting the most appropriate design (treatment train) to scale up from pilot to the field scale has limited its practical application. The economic feasibility of the selected technologies was critically analyzed and the future research prospects of resource recovery from wastewater have been outlined in this review.