De novo homozygous deletion of segmental KAL1 and entire STS cause Kallmann syndrome and X-linked ichthyosis in a Chinese family
ABSTRACT: Kallmann syndrome is a genetically heterogeneous condition and a treatable form of male infertility. Defects in KAL1 gene have been implicated in Kallmann syndrome, which can be associated with X-linked ichthyosis in contiguous gene syndromes. In order to uncover the genetic cause of two brothers with Kallmann syndrome and X-linked ichthyosis, a custom semiconductor targeted resequencing panel to detect seventeen Kallmann syndrome causal genes and STS gene was designed. Next-generation sequencing was performed using this panel in the two affected brothers and their normal parents. To validate the result, we applied CytoScan™ HD array, quantitative real-time PCR and direct PCR electrophoresis analysis with the participants. The patients received clinical assessment, human chorionic gonadotropin treatment and follow-up for 39 months. The results showed that the two affected siblings have the same de novo deletion at Xp22.3 including exons 9-14 of KAL1 gene and entire STS gene but showed different phenotypes in some respects. The secondary sex characteristics of the patients were greatly improved after treatment. We firstly reported that a de novo homozygous deletion contribute to KS with bilateral cryptorchidism and unilateral renal agenesis or normal kidney development and developed a cost-effective and reliable semiconductor targeted resequencing panel for genetic diagnosis of Kallmann syndrome in routinely obtained samples. One of the two brothers with Kallmann syndrome and X-linked ichthyosis was analyzed for validation the results of the deletion detected by next-generation sequencing.
Project description:To characterize Homologous recombination deficiency (BRCAness) in triple-negative breast cancer PDX models genomic signature was utilized. After normalization using ChAS we obtained absolute copy number profiles using the GAP software (Popova et al, Genome Biol, 2009). The number of Large-scale State Transitions (LSTs) was used to annotate PDX as BRCAness or not (Popova et al, Cancer Res 2012).
Project description:To characterize Homologous recombination deficiency (BRCAness) in triple-negative breast cancer PDX models genomic signature was utilized. After normalization using Genotyping Console we obtained absolute copy number profiles using the GAP software (Popova et al, Genome Biol, 2009). The number of Large-scale State Transitions (LSTs) was used to annotate PDX as BRCAness or not (Popova et al, Cancer Res 2012).
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