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Diagnosing Down Syndrome, Cystic Fibrosis, Tay-Sachs Disease And Other Genetic Disorders
Sometimes, a pediatrician will suspect that a child has a genetic disorder based on the child's symptoms or on the presence of dysmorphic features. For example, if a child has coarse facial features and developmental delays, a pediatrician may have reason to believe that the child has a form of mucopolysaccharidosis. Mucopolysaccharidosis is a family of diseases caused by an enzyme deficiency that leads to the accumulation of glycosaminoglycans (GAGs) within the lysosomes of cells. In one particular variant of this disease known as mucopolysaccharidosis I (MPS I), a deficiency of the enzyme alpha-L-iduronidase causes a build up of GAGs in tissues and organs, which in turn leads to a host of signs including skeletal deformities, coarse facial features, enlarged liver and spleen, and mental deficiencies. Because of the progressive nature of MPS I, a child might not exhibit noticeable symptoms until one to three years of age or even later, depending on severity.
There are a number of reasons that a pediatrician might refer a child to see a geneticist. Geneticists can confirm or rule out a physician's diagnosis based on the findings of a physical exam and various tests. In the case of a child with suspected MPS, if the enzymatic deficiency associated with the disorder is confirmed via testing, DNA analysis may also be performed to determine the exact genetic mutation causing the disorder. Because MPS I is inherited in an autosomal recessive fashion, identification of the mutation can allow the family to undergo carrier screening, as well as prenatal or preimplantation diagnosis in any future children.Genetic Testing And Genetic Counseling For Schwannomatosis
Genetic testing for schwannomatosis is available and may be appropriate for some people. The current test identifies a mutation in the SMARCB1 gene, which predisposes an individual to developing the disorder. Because some cases of schwannomatosis are not caused by a mutation in the SMARCB1 gene – and inheritance patterns for the disorder are complex – genetic testing is not always conclusive.
Advanced Genetic Testing for Schwannomatosis at the UAB Medical Genomics LaboratoryGenetic testing directly sequences the SMARCB1 gene to identify mutations associated with schwannomatosis. The UAB Medical Genomics Laboratory offers the most scientifically reliable and advanced genetic testing techniques currently available for the diagnosis and characterization of SMARCB1 mutations. This state-of-the-art laboratory performs the highest volume of neurofibromatosis genetic testing in the world and has also developed the most widely used approach to testing.
Genetic testing for schwannomatosis might be appropriate for the following individuals:
A genetic counselor – who has specialized training in medical genetics and counseling – can help families make informed decisions about whether genetic testing right for them. The UAB Neurofibromatosis Program provides access to a team of experienced genetic counselors who can help families learn more about genetic testing for schwannomatosis and provide support to assist in adapting to a new diagnosis.
Also, a genetic counselor can provide information and guidance in the following key areas:
Cell Catalogue Of Genetic Developmental Disorders
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By analysing the "molecular speed", the researchers discovered that mutations in certain genes (here: SOX9) lead to cells, e.G. Of the limbs, that do not develope properly during embryogenesis.
view moreCredit: Huang, X., Henck, J., Qiu, C. Et al. Single-cell, whole-embryo phenotyping of mammalian developmental disorders. Nature 623, 772–781 (2023). Https://doi.Org/10.1038/s41586-023-06548-w
Researchers often need many years to gain new insights into congenital genetic defects and the resulting malformations and disorders. Using single-cell sequencing, the Lübeck geneticist Malte Spielmann, Professor of Human Genetics at the University of Lübeck and Director of the Institute of Human Genetics at the University Medical Centre Schleswig-Holstein, Campus Lübeck and Kiel, together with an international research team, has succeeded in identifying the effects of specific mutations at molecular and cellular level in a single experiment involving more than 1.5 million cells. The resulting cell catalogue includes data on mutations and their effects on development at an unprecedented breadth and resolution.
As genetic disorders often occur during early pregnancy, they cannot be analysed in human embryos or cell cultures. Mouse models are often used in research for this purpose. Thanks to the development of modern technologies for the targeted modification of genetic material, such as CRISPR/Cas9, genetically manipulated mice, so-called "knockout" mice, can be produced much faster and with greater accuracy. However, current technologies for the analysis and characterisation of embryonic malformations operate at a very low throughput, are extremely labour-intensive and it often takes several years to study a single knockout mouse. Methods with the sensitivity and throughput required to analyse complex organ systems such as a developing brain are still lacking.
The aim of the new study was therefore to use single-cell RNA sequencing to establish an alternative method for analysing embryonic malformations in the mouse model. An international research team led by Professor Malte Spielmann from the University of Lübeck and the University Medical Centre Schleswig-Holstein in Germany investigated the gene expression of over 100 mouse embryos with 25 different genetic alterations in a single large experiment. A study on this scale would have taken countless years using conventional methods. The resulting single-cell atlas of fetal gene expression enables to research and identify different cell types responsible for embryonic malformations.
Prof Spielmann compares the promise of the technology to the effect of the Hubble Space Telescope. "Single cell methods - you can't overestimate their importance for understanding developmental biology," he says. "They really give us a picture that we've never seen before. I am convinced that this new approach will allow us to find even the smallest cellular changes that were previously overlooked, which will help us to better understand the development of embryonic malformations and thus identify potential targets for future therapies."
To analyse the data, the authors developed new computer algorithms allowing to reconstruct the information about each individual cell on the computer. They not only succeeded in grouping the cells according to type and subtype, but also in tracing their developmental pathways and detecting minimal cellular differences and changes. Using this method, the scientists identified 77 main cell types and around 650 cell subtypes. Another major advantage of this new approach is the significantly reduced number of animals used for this analysis, as only a single experiment was carried out and all further analyses were performed in silico, i.E. On the computer.
Method of ResearchExperimental study
Subject of ResearchAnimals
Article TitleSingle-cell, whole-embryo phenotyping of mammalian developmental disorders
Article Publication Date15-Nov-2023
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