Biomedical subjects

Judith Armstrong

Publications and source records attributed to Judith Armstrong.

5 recordsLinked to original sources

PubMed2026

Identification of autosomal and sex chromosome aneuploidies using next generation sequencing.

MOTIVATION: Chromosomal abnormalities, referred to as aneuploidies, occur in approximately 0.3% of live births. While the majority of aneuploidies in humans are incompatible with life, well-characterized exceptions include Down syndrome (47,+21), Patau syndrome (47,+13), Edwards syndrome (47,+18), Turner syndrome (45,X0), Klinefelter syndrome (47,XXY), and triple X syndrome (47,XXX). These chromosomal alterations disrupt gene expression and cellular function, leading to genetic and developmental disorders. With the increasing adoption of next generation sequencing (NGS) in clinical diagnostics, this study aims to explore the potential use of NGS for aneuploidies detection. RESULTS: Using data derived from clinical exomes (CES) and whole exomes (WES) sequencing we have been able to detect autosomal as well as sex chromosome aneuploidies with high specificity. Moreover, we have also been able to identify mosaic aneuploidies proving the high sensibility of this methodological approach. Thus, we present NGS as a cost-effective first line approach to detect chromosomal aneuploidies in routine diagnostic practice. AVAILABILITY AND IMPLEMENTATION: Scripts are available at https://github.com/B-R-I-D-G-E/AneuploidiesStudies.

Humans↗

PubMed2006

The X-linked methyl binding protein gene Kaiso is highly expressed in brain but is not mutated in Rett syndrome patients.

Rett syndrome (RTT; OMIM 312750) is an X-linked dominant neurological disorder, which affects mostly females. It is associated with mutations of the MECP2 gene, codifying for a methyl-CpG DNA binding protein of the MBDs family, sharing the common Methyl Binding Domain. MeCP2 binds single methylated CpG pair and brings transcriptional silencing to the substrate DNA templates. However, around 5-10% of clinically well defined RTT patients do not show any mutations in this gene. Several hypotheses have been postulated to clarify the remaining unexplained RTT cases. We pointed our attention on Kaiso gene. This gene is localized in the Xq23 region and codifies for a protein acting as a methyl-CpG binding protein by using three zinc-finger domains: for this reason it is not strictly related to the MBD family of proteins, even if it may repress transcription of methylated genes as well. To investigate the potential association of Kaiso disfunction with pathogenesis of Rett syndrome, we approached the analysis at two different levels. Primarily, we performed an itemized murine brain expression analysis of Kaiso gene. Expression data and localization made it an excellent candidate as additional causative gene for MECP2 negative, classical RTT patients. On the bases of this data a detailed mutational analysis of 44 patients from Spanish, UK, and Italian archives has been performed to the coding region of Kaiso. No mutation was found while a very frequent polymorphism was identified and characterized. Our study suggests that this gene is not implicated in the RTT molecular pathogenesis, but additional analyses are needed to exclude it as causative gene for X-linked mental retardation disorders.

Animals↗

PubMed2005

Giant SCA8 alleles in nine children whose mother has two moderately large ones.

We report here a family in which each of nine children has inherited giant SCA8 CTG expansions from a homozygous mother who has two moderately large SCA8 CTG alleles. In contrast, three homozygous male individuals and a case of coexistence of two expansions of the FRDA gene and one of SCA8, all of them with moderately large alleles, have transmitted their respective SCA8 expanded alleles with minor changes, as usually occurs in heterozygous male transmissions.

Adult↗

PubMed2004

The impact of MECP2 mutations in the expression patterns of Rett syndrome patients.

Rett syndrome (RTT), the second most common cause of mental retardation in females, has been associated with mutations in MeCP2, the archetypical member of the methyl-CpG binding domain (MBD) family of proteins. MeCP2 additionally possesses a transcriptional repression domain (TRD). We have compared the gene expression profiles of RTT- and normal female-derived lymphoblastoid cells by using cDNA microarrays. Clustering analysis allowed the classification of RTT patients according to the localization of the MeCP2 mutation (MBD or TRD) and those with clinically diagnosed RTT but without detectable MeCP2 mutations. Numerous genes were observed to be overexpressed in RTT patients compared with control samples, including excellent candidate genes for neurodevelopmental disease. Chromatin immunoprecipitation analysis confirmed that binding of MeCP2 to corresponding promoter CpG islands was lost in RTT-derived cells harboring a mutation in the region of the MECP2 gene encoding the MBD. Bisulfite genomic sequencing demonstrated that the majority of MeCP2 binding occurred in DNA sequences with methylation-associated silencing. Most importantly, the finding that these genes are also methylated and bound by MeCP2 in neuron-related cells suggests a role in this neurodevelopmental disease. Our results provide new data of the underlying mechanisms of RTT and unveil novel targets of MeCP2-mediated gene repression.

Blotting, Western↗

PubMed2001

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