New thesis on skeletal dysplasias

Anna Hammarsjö from the group Rare Diseases will defend her thesis "Expanding the genetic and phenotypic spectrum of skeletal dysplasias" on September 7, 2018. Main Supervisor is Giedre Grigelioniene.

What's the main focus of your thesis?

This thesis focuses on gene discovery, studies of previously clinically defined skeletal dysplasias with unknown genetic background and aims to improve the molecular analyses for patients with diagnoses which are difficult to solve. Clinical diagnosis of skeletal dysplasias is based on meticulous phenotypic characterization, skeletal radiography (for pattern recognition) and genetic testing. Molecular diagnostics has improved significantly by massively parallel sequencing (MPS) technologies, such as whole exome and genome sequencing.

Which are the most important results?

We have identified new genes that are important for skeletal function and previously not known to be associated with skeletal disorders. Further, we have identified mutations in known skeletal dysplasia genes, with additional phenotypes – extending the clinical and molecular spectrum of skeletal disorders. Altogether, we show that massively parallel sequencing makes molecular diagnoses easier and that whole genome sequencing is a good way to, not only find single nucleotide variants, but also structural variants. As well as, that RNA is necessary to improve molecular diagnostics and reveal if a variant leads to aberrant splicing.

How can this new knowledge contribute to the improvement of people’s health?

Molecular diagnosis is important since it gives information about prognosis and recurrence risk, as well as, in some cases possibilities to offer targeted treatment, participation in clinical trials, and tailored medical follow-up. Further, we learn from disease and in the long run this new knowledge can lead to therapeutics for common skeletal disorders, such as osteoporosis and arthrosis.

What are your future ambitions?

I will in October start working as an associate clinical laboratory geneticist at the department for Clinical Genetics at Karolinska University Hospital and hope to be able to continue with research within the field.

Dissertation

Friday September 7, 2018 at 09:00 Nanna Svartz, J3:12, Bioclinicum, Karolinska University Hospital Solna

Thesis

Expanding the genetic and phenotypic spectrum of skeletal dysplasias