Variante patogénica homocigótica del gen BBS10 en un paciente con síndrome de Bardet-Biedl / A pathogenic homozygous variant of the BBS10 gene in a patient with Bardet Biedl syndrome

Resumen El síndrome de Bardet-Biedl es una enfermedad hereditaria, autosómica recesiva, con gran heterogeneidad de locus, que pertenece a las denominadas ciliopatías, denominadas así por la deficiencia funcional presente y porque las proteínas afectadas se localizan en el cilio primario. El síndrome afecta múltiples sistemas, con compromiso visual, renal, cognitivo, esquelético y gonadal, y obesidad. Este síndrome presenta una gran variabilidad intrafamiliar e interfamiliar. Se presenta el caso clínico de un paciente adolescente con diagnóstico de síndrome de Bardet-Biedl, así como su manejo, los resultados de la secuenciación de 22 genes y el análisis actualizado de la literatura médica. Se recopiló la información clínica y, previo consentimiento informado, se hizo la prueba de panel de secuenciación multigénica de los genes implicados. El paciente es hijo de la unión de personas consanguíneas. Fue el primer afectado en la familia y presentaba polidactilia posaxial, obesidad, micropene, retinitis pigmentaria y dificultades de aprendizaje. En el panel multigénico, se identificó la variante patogénica homocigótica c.39_46del en el gen BBS10 y otras variantes de genes BBS asociadas con la obesidad. Dado que el síndrome de Bardet-Biedl es una enfermedad huérfana rara, interpretar el pleiotropismo y la heterogeneidad de locus y de alelos, constituye un reto. La confirmación molecular permite el manejo adecuado de los pacientes, así como el seguimiento y el asesoramiento genético apropiados.

Abstract The Bardet-Biedl syndrome is an autosomal recessive hereditary disorder with vast locus heterogeneity that belongs to the so-called ciliopathies, whose proteins are localized in the primary cilia and present functional deficiency. The multisystemic features of the disease include ocular, renal, cognitive, skeletal, as well as gonadal involvement and obesity, among others, with high inter- and intrafamilial variability. We describe the clinical case of an adolescent male patient with Bardet-Biedl syndrome, including the approach, the results from a 22-gene sequencing panel, and the analysis of updated scientific literature. We collected the clinical data of the patient and, after obtaining the informed consent, we conducted a multigenic sequencing panel oriented to known implicated genes. The patient was born to consanguineous parents and was the first affected member of the family. He presented with postaxial polydactyly, obesity, micropenis, retinitis pigmentosa, and learning disability. The multigenic panel allowed the identification of the homozygous pathogenic variant c.39_46del in the BBS10 gene and in other BBS genes variants associated with obesity. As the Bardet-Biedl syndrome is a rare disease, it is challenging to interpret its pleiotropism and gene/allelic heterogeneity. Its confirmation by molecular tests allows an adequate approach, follow-up, and genetic counseling of the patient and the family.

Screening and cloning of genes related to varicose great saphenous vein accompanying with primary deep vein valve insufficiency / 中华外科杂志

<p><b>OBJECTIVE</b>To screen the genes related to the occurrence and development of varicosis of the great saphenous vein in the patients with primary deep vein valve insufficiency.</p><p><b>METHODS</b>Using mRNA fluorescent differential display reverse transcriptive polymerase chain reaction (FDD-RTPCR), different genes expressed in the varicose great saphenous veins in patients with primary deep vein valve insufficiency and corresponding normal human tissues were compared. Differentially expressed cDNA fragments confirmed by Northern blot were compared and then cloned into the pGEM-Teasy vector. Positive clones were selected and sequenced. All the sequences were put into GenBank and analyzed by BLASTN software to search for their genetic origins.</p><p><b>RESULTS</b>Altogether 37 different cDNA fragments were obtained and 30 of which were confirmed by Northern blot. Analysis of the sequences by BLASTN software showed that C(610) fragment (NO. 18 cDNA clone) shared 96% homology with the mRNA sequence of the human Mckusick-Kaufman syndrome gene (MKKS gene).</p><p><b>CONCLUSION</b>C(610) fragment is highly homologous with the mRNA sequence of the human MKKS gene and is closely related to the development of varicosis of the great saphenous vein in patients with primary deep vein valve insufficiency.</p>