Biology subjects

Rodriguez-Laguna, L.

Publications and source records attributed to Rodriguez-Laguna, L..

2 recordsLinked to original sources

bioRxiv2018

Familial hypercholesterolemia: a single-nucleotide variant (SNV) in mosaic at the Low density lipoprotein receptor (LDLR)

IntroductionFamilial hypercholesterolemia (FH) is most frequently caused by genetic variants in the LDLR gene. Most of LDLR pathogenic variants are missense, followed by splicing and deletion/insertions variants. Mosaicism is a genetic condition in which an individual shows more than one clone of cells with different genotypes.\n\nObjectiveMolecular characterization of a patient with hypercholesterolemia.\n\nMethodsGenetic analysis of DNA from peripheral blood and saliva was performed by NGS, sanger sequencing and pyrosequencing technologies.\n\nResultsNGS analysis detected the pathogenic variant LDLR:c.1951G>T:p.(Asp651Tyr) in 9%-12% of reads. The presence of the variant was confirmed by pyrosequencing analysis.\n\nConclusionHerein, we report the first case of a mosaic single nucleotide variant affecting the LDLR gene in a patient with familial hypercholesterolemia. As has been described for other pathologies, mosaicism could be underestimated in FH and its detection will improve with the introduction of NGS technologies in the diagnostic routine.

genetics↗

bioRxiv2017

CLAPO syndrome: Identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype

BackgroundCLAPO syndrome is a rare vascular disorder characterized by Capillary malformation of the lower lip, Lymphatic malformation predominant on the face and neck, Asymmetry, and Partial/generalized Overgrowth. Although the genetic cause is not known, the tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism.\n\nSubjects and methodsWe clinically evaluated a cohort of 13 patients with CLAPO and screened 20 DNA blood/tissue samples from nine patients using high-throughput, deep sequencing.\n\nResultsWe identified five activating mutations in the PIK3CA gene in affected tissues from six of the nine patients studied; one of the variants (NM_006218.2:c.248T>C; p.Phe83Ser) has not been previously described in developmental disorders.\n\nConclusionsWe describe for the first time the presence of somatic activating PIK3CA mutations in patients with CLAPO. We also report an update of the phenotype and natural history of the syndrome.

genetics↗