Constitutional Genetics

woman in genetics lab

Head of Section – Kath Smith 0114 226 0743

The Constitutional team consists of 16 registered scientists who each specialise in specific genetic service areas. We offer specialist services for developmental disorders, reproductive genetics, connective tissue disorders, neurogenetic disorders, inborn errors of metabolism and haemostasis, haemoglobinopathies and haemochromatosis.

Our clinical scientists work closely with the referring clinicians and, in cases where known genetic rearrangements or mutations exist and family studies are required, with our Clinical Genetics team.

Diagnostic testing is available for a wide range of both common and rare genetic conditions affecting neonates, children and adults. Predictive and prenatal testing is also available for a number of conditions through our Clinical Genetics service.

We are continuously expanding our range of tests including introducing new, and updating our current, next generation sequencing panels. Please look at our A-Z List of Genetic Tests (PDF) for further information. If you cannot find the genetic test you are interested in, please contact us to discuss what we can offer. All discussion is welcomed!

Find out more about how to package and send samples to our labs. We accept referrals from the UK and abroad.


Developmental disorders

Array CGH (microarray) testing is offered as a first line service for paediatric referrals with developmental delay and/or multiple congenital abnormalities and for autism.

SYNGAP1 full-gene sequencing for SYNGAP1-related non-syndromic intellectual disability is also available.

Karyotyping (chromosome analysis) is provided for the detection of chromosome aneuploidy, balanced and unbalanced chromosomal rearrangements and mosaicism for chromosome aneuploidy in neonates, children and adults.

We offer a comprehensive suite of single locus micro-deletion (or duplication) FISH tests known to be associated with specific syndromes, as well as a rapid aneuploidy FISH service for the detection of trisomy for chromosomes 21, 13, 18 and aneuploidy of the sex chromosomes X and Y.

We also perform chromosomal instability testing for Ataxia Telangiectasia, Fanconi Anaemia and Blooms syndrome.

See the Full A-Z List of Genetic Tests.

Contact Josh Willoughby (0114 271 7284)
Contact Kath Smith (0114 226 0743)

Connective tissue disorders

The connective tissue disorders (CTD) service is a rapidly expanding service offering testing for autosomal dominant and autosomal recessive osteogenesis imperfecta (OI), Ehlers-Danlos syndrome (EDS) and other connective tissue disorders including pseudoxanthoma elasticum, hypophosphatasia and familial porencephaly.

Testing includes full gene sequencing and dosage analysis on individual genes, along with predictive and prenatal testing for known family mutations.

We have recently increased our range of testing to include Next Generation Sequencing. This technique uses panels of genes to simultaneously screen genes associated with a specific phenotype.

View the Full A-Z List of Genetic Tests to see which genes/panels are available for testing and visit the Next Generation Sequencing (NGS) page for information about our live connective tissue disorder NGS panels.

Please note: we no longer offer medico-legal testing for these conditions.

Contact Renarta Crookes (0114 226 0599)
Contact Harveer Cheema (0114 271 7019)
Contact Duncan Baker (0114 271 7041)

Haemostasis, haemoglobinopathy and haemochromatosis

We offer comprehensive molecular genetic analysis for a rapidly expanding group of bleeding, clotting and platelet disorders, Fanconi Anaemia and bone marrow failure/aplastic anaemia, alpha and beta-thalassaemias, sickle cell disease plus hereditary haemochromatosis.

DNA sequence analysis using next generation and Sanger sequencing along with dosage analysis by MLPA (where necessary) are available.

Haemostasis disorders include haemophilia A and B, von Willebrand disease, and deficiencies of antithrombin, protein C and protein S. Our Next Generation sequencing panel includes 13 of the commonly analysed haemostasis and platelet bleeding disorder genes.

We provide Next Generation Sequence analysis of all 16 known complementation groups responsible for Fanconi Anaemia (following a positive chromosome breakage test) and several further genes associated with bone marrow failure/aplastic anaemia will be available shortly.

View the Full A-Z List of Genetic Tests to see which genes/panels are available for testing.

Contact Nikolas Niksic (0114 271 7021)

Inborn errors of metabolism

We offer testing for an extensive range of inherited metabolic disorders, testing for common mutations, full gene screens, or gene panels as appropriate. Areas covered include newborn screening, glycogen storage diseases, fatty acid metabolism disorders, Wilson disease, peroxisomal disorders, urea cycle disorders and familial hypercholesterolaemia.

We work closely with the metabolic section of the Trust’s Clinical Chemistry Department and the Metabolic Medicine team to provide comprehensive diagnostic services.

We also provide a diagnostic service as part of the National Diagnostic and Management Centre for McArdle disease and related disorders. We offer direct-access hotspot mutation testing for McArdle disease, as well as a Next Generation Sequencing panel for metabolic myopathies/rhabdomyolysis.

View the Full A-Z List of Genetic Tests to see which genes/panels are available for testing and visit the Next Generation Sequencing (NGS) page for information about our live inborn errors of metabolism NGS panels.

Contact Mandy Nesbitt (0114 226 0584)
Contact Richard Kirk (0114 305 3641)

Neurogenetic disorders

This service offers diagnostic testing for children and adults, by gene sequencing, dosage analysis and DNA fragment analysis for mutations in a variety of genes involved with neurological conditions.

Our close links with specialist neurologists and research groups and many years experience of genetic testing for neurological disorders makes us highly specialised in this area of genetic diagnostics and enables us to offer a high level of support and expertise to referring clinicians. Please do not hesitate to contact one of our scientists (see below) if you have any questions about the service.

Our flagship Hereditary Spastic Paraplegia (HSP) service has been running for over 12 years. Over this period we have moved from offering single gene analysis to dosage analysis by MLPA and we are now able to test for a full panel of 41 genes associated with HSP which we are expanding as new genes come to light.

Other tests available within our section include a range of neurological conditions such as spinal muscular atrophy, Huntington’s disease, Friedreich ataxia, episodic ataxia and a number of spinocerebellar ataxias. Please see the Full A-Z List of Genetic Tests for a comprehensive list of all tests available.

All of our testing is available both nationally and internationally and we now offer a series of Next Generation Sequencing panels for a range of disorders:

  • Dystonia/Parkinsonism NGS panel
  • FALS/Dementia NGS panel
  • Episodic ataxia NGS panel
  • Familial Hemiplegic Migraine NGS panel
  • Hereditary Spastic Paraplegia NGS panel
  • Hereditary Ataxia NGS panel

View the Full A-Z List of Genetic Tests to see which genes/panels are available for testing and visit the Next Generation Sequencing (NGS) page for information about our live neurological disorders NGS panels.

Contact Nick Beauchamp (0114 226 0599)
Kate Garrard (0114 305 3641)

Reproductive genetics

Prenatal diagnosis for chromosome abnormality is offered in pregnancies that are identified as being at high risk of a chromosome abnormality through the Down syndrome screening programme, fetal anomaly scanning or having a family history of a chromosome abnormality. Testing is carried out on amniotic fluid, chorionic villus or fetal blood samples referred from the local region.

A rapid screen by Fluorescent in-situ Hybridisation (FISH) to detect aneuploidy of chromosomes 13,18,21, X and Y is offered, along with a full karyotyping service. In addition, all referrals with outflow heart defects are screened using a locus specific gene probe for deletion of the q11.2 region of chromosome 22.

Molecular prenatal diagnosis is available for disorders offered by all areas of the genetics service and must always be arranged through the Clinical Genetics Service. It is essential that the initial diagnosis has been clearly established and mutation(s) identified in the affected individual and parent(s), preferably well in advance of any request for prenatal testing. All molecular prenatal testing includes assessment of maternal cell contamination of the fetal material using a highly polymorphic marker panel.

From 1 November 2016, parental blood samples are no longer be accepted from couples with isolated pregnancy loss or recurrent miscarriage but cytogenetic analysis can be performed on products of conception from the third and subsequent consecutive miscarriages. Parental blood samples will be accepted where: (1) testing of products of conception revealed an unbalanced structural fetal karyotype or (2) after pregnancy loss of a fetus with multiple congenital abnormalities or severe intrauterine growth restriction (IUGR), where material from the fetus or placenta is unavailable for cytogenetic testing.

Testing for chromosome abnormality for tissue samples following pregnancy loss or at post mortem examination is now by array CGH (microarray) on fetal loss or viable post mortem material. We also process paraffin section slides for aneuploidy FISH where fresh post mortem material is not available and offer testing for specific requests such as investigation of chromosome mosaicism.

See the Full A-Z List of Genetic Tests.

Testing assumes that appropriate consent has been obtained for the analysis. If this is not the case the laboratory must be contacted to discuss the matter further.

Contact Emma Sheering (0114 271 7009)
Contact James Steer (0114 271 7009)

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