RESUMEN
BACKGROUND: This study aims to show the clinical and biochemical features in patients with severe hypertriglyceridemia (HTG) associated with rare variants in the apolipoprotein A-V (APOA5) gene. MATERIALS AND METHODS: Demographics, blood lipid levels, body mass index (BMI) and APOA5 mutation subtypes were collected from the endocrinology clinic registry and analyzed for a retrospective cohort study of ten patients with severe HTG and APOA5 gene variants. RESULTS: Of the 10 cases, four were female, and six were male. The median age was 45.0 years (min-max: 21-60 years), the median triglyceride (TG) was 2429.5 mg/dL (27.5 mmol/L) (min-max: 1351-4087 mg/dL, 15.3-46.2 mmol/L), and the mean BMI was calculated as 30.4 ± 4.4 kg/m2 (min-max: 24.9-41.0 kg/m2). Four cases had diabetes mellitus (DM); two were on intensive insulin therapy, and two were on basal insulin therapy. The mean hemoglobin A1c (HbA1c) was 9.2 ± 1.2 % (min-max: 8.3-11.0 %). Among the study group, eight different APOA5 gene mutations were detected. These variants were heterozygous in 2 patients and homozygous (bi-allelic) in 8 patients. One patient was homozygous for APOA5 p.Ser19Trp, a relatively common polymorphism that is a risk variant for HTG. CONCLUSION: We report a cohort of patients with biallelic and single copy APOA5 variants, who were diagnosed later in life. Most had secondary factors such as DM, or obesity with increased BMI. Most rare APOA5 variants found in our patients were of uncertain significance. Our results add to the growing evidence that rare variants in certain candidate genes may predispose to developing HTG, together with secondary factors such as obesity. The genetic basis of HTG in many other patients is still unknown and remains the subject of further investigation.
Asunto(s)
Proteínas Portadoras/genética , Diarrea Infantil/diagnóstico , Diarrea Infantil/genética , Retardo del Crecimiento Fetal/diagnóstico , Retardo del Crecimiento Fetal/genética , Predisposición Genética a la Enfermedad , Enfermedades del Cabello/diagnóstico , Enfermedades del Cabello/genética , Mutación , Piodermia Gangrenosa/diagnóstico , Piodermia Gangrenosa/genética , Alelos , Biomarcadores , Facies , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Inmunofenotipificación , Lactante , Linfocitos/inmunología , Linfocitos/metabolismo , Piel/patologíaRESUMEN
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Asunto(s)
Humanos , Femenino , Lactante , Proteínas Portadoras/genética , Diarrea Infantil/diagnóstico , Diarrea Infantil/genética , Retardo del Crecimiento Fetal/diagnóstico , Retardo del Crecimiento Fetal/genética , Predisposición Genética a la Enfermedad , Enfermedades del Cabello/diagnóstico , Enfermedades del Cabello/genética , Piodermia Gangrenosa/genética , Biomarcadores/sangre , Estudios de Asociación Genética , Piodermia Gangrenosa/diagnóstico , Mutación , Genotipo , Alelos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Inmunofenotipificación , Linfocitos/inmunología , Linfocitos/metabolismo , Piel/patologíaRESUMEN
New array technologies have facilitated the analysis of submicroscopic chromosomal imbalances and structural variants. Copy number variation (CNV) analysis can reveal genetic imbalances in up to 10% of cases involving intellectual disability (ID), with or without multiple congenital anomalies (MCA). Here we present 4 cases, diagnosed by CNV analysis using Affymetrix Genome Wide Human SNP 6.0 array, and their parents. CNVs ranging from 18 to 196 per subject, with a size range of 100kb- 6093kb, were detected in all cases. One case revealed inherited CNVs, whilst de novo ins/dels were found in the other three which may be causative factors in the development of clinical pictures. Microarray technology may help to reveal the etiology of ID and is a potentially useful diagnostic tool for patients with ID/MCA.
Asunto(s)
Anomalías Múltiples/genética , Variaciones en el Número de Copia de ADN/genética , Genoma/genética , Discapacidad Intelectual/genética , Niño , Femenino , Técnicas de Genotipaje , Humanos , Lactante , MasculinoRESUMEN
Caudal appendage is a rare dysmorphic feature of which etiologic mechanisms are not well understood. Here we report monozygotic (MZ) twin brothers who are discordant for the caudal appendage and multiple congenital anomalies. Twins were the product of a 33 weeks of gestation, monochorionic-diamniotic pregnancy. On admission the proband had micrognathia, beaked nose, hypospadias, caudal appendage and juxtaductal aorta coarctation. At birth, he was small for gestational age and he had transient hypothyroidism which was detected in the newborn period. Karyotype analysis showed 46,XY. Monozygosity was shown by 15 microsatellite markers plus amelogenin (AmpFlSTR Identifiler PCR Amplification Kit, Applied Biosystems). Genome-wide copy number analysis of the twins by DNA-DNA hybridization of whole genomic DNA (NimbleGen Human CGH 385K WG-T v2.0 array) showed a significant difference at two neighboring probes with Log2 ratio: 0.72088 which are located on chromosome 3p12.3. Further analysis by high resolution of chromosome 3 array (Roche NimbleGen Human HG18 CHR3 FT Median Probe Spacing 475 bp) and quantitative PCR analysis did not confirm the deletion.
