RESUMEN
PURPOSE: This study presents a case of familial transmission of thyroxine-binding globulin (TBG) deficiency. The SERPINA7-gene which codes for TBG is located on the X-chromosome (Xq21-22). More than 45 mutations have been reported to cause TBG- deficiency from various countries, but none from India so far. Genetic analysis of SERPINA7 gene was carried out to determine the cause of low TBG levels in one family. METHODS: DNA samples of the propositus and the family members were subjected to Polymerase Chain Reaction (PCR) followed by direct sequencing. Allele-specific PCR and Next-gen sequencing (NGS) were employed to confirm the site of the mutation. Thyroid function tests were estimated by Radioimmunoassay (RIA) and Immunoradiometric assay (IRMA) kits. X-chromosomal inactivation status was analyzed in the female members harboring the mutation. RESULTS: A mutational screening in this family revealed a novel frame-shift mutation S353Q, 354fs3X in the exon 4 of the SERPINA7 gene which will be referred to as TBG-complete deficiency-India (TBG-CD-Ind). One out of four female family members harboring the mutation showed selective X-chromosomal inactivation. The affected family members were clinically euthyroid initially, showed changes in the thyroid function when tested after a long time span. However, the changes in the thyroid function in the affected family members had an autoimmune etiology. CONCLUSION: This study presents the first report of TBG-CD from India wherein a novel frameshift mutation referred to as TBG-CD-Ind (S353Q, 354fs3X) in the SERPINA7 gene was detected. No apparent association was identified between thyroid function and the TBG-mutation in the affected subjects. A detailed biochemical and genomic testing to determine the exact cause of discordant TFT in the patients would certainly aid in the unequivocal diagnosis of the thyroid function and for the precise individualized treatment.
Asunto(s)
Globulina de Unión a Tiroxina/análisis , Globulina de Unión a Tiroxina/deficiencia , Globulina de Unión a Tiroxina/genética , Adulto , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X/sangre , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , India , Masculino , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa/estadística & datos numéricos , Pruebas de Función de la Tiroides/métodos , Pruebas de Función de la Tiroides/estadística & datos numéricos , Secuenciación del Exoma/métodos , Secuenciación del Exoma/estadística & datos numéricosRESUMEN
The prevalence of non-communicable diseases like diabetes mellitus (DM) and hypertension (HTN) is growing worldwide. Both lead to nephropathy if not controlled effectively. Microalbuminuria (MAU) is recognized as an early predictor for nephropathy. Additionally, the timely detection of advanced glycation end products (AGEs) is also considered to be an important prognostic factor for diabetic nephropathies. Hence, screening for the early detection of MAU and AGEs would be an useful and relatively inexpensive laboratory test for early clinical diagnosis for the incidence of nephropathy in these diseases. This study was conducted in DM, HTN and pregnancy induced hypertensive (PIH) subjects. MAU and Nε-Carboxymethyllysine (CML) levels were estimated by in-house RIA kits in the patient groups and controls, while the total AGEs level in serum was determined by ELISA. The levels of MAU, CML and AGE-BSA were observed to be significantly higher in DM, HTN and PIH subjects compared to controls (p < 0.001). Increased serum CML and AGEs levels in DM, HTN and PIH subjects indicated ongoing glycemic damage and their susceptibility to develop renal complications.
