Rare Disease

SNP array testing is offered as a first line service for paediatric referrals with developmental delay and/or multiple congenital abnormalities and for autism.

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.

Whole Genome Sequencing is also available for patients with congenital malformations and  dysmorphisms, intellectual disability, hypotonic infants  and for parental sequencing for lethal recessive disorders where there is limited or no DNA from the deceased.

The Musculoskeletal (MSK) 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 and NGS panels, along with predictive and prenatal testing for known family mutations.

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

We offer comprehensive molecular genetic analysis for a rapidly expanding group of bleeding, clotting and platelet disorders, iron metabolism 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.

In addition single gene sequencing is available for haemostasis disorders including haemophilia A and B, von Willebrand disease, and deficiencies of antithrombin, protein C and protein S.

This service offers testing of children and adults for monogenic familial hypercholesterolaemia by NGS and dosage and also includes analysis of the polygenic form of the disease.

We offer genetic testing relating to newborn screening for cystic fibrosis (in addition to diagnostic/carrier testing), medium chain acyl CoA dehydrogenase (MCAD) deficiency, glutaric aciduria type 1 (GA1) and isovaleric acidaemia (IVA).

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 14 years. Over this period we have moved from offering single gene analysis, introducing dosage analysis by MLPA to offering a large panel of genes associated with HSP to detect both point mutations and large deletions and duplications.

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.

We offer Next Generation Sequencing or Whole Genome Sequencing panels for a range of disorders:

• Dystonia, chorea and other movement disorders
• Neurodegenerative disorders including ALS, dementia and Parkinson disease
• Paroxysmal central nervous system disorders including Episodic ataxia and Familial Hemiplegic Migraine
• Hereditary spastic paraplegia
• Hereditary ataxia
• Hereditary neuropathy
• Spinal muscular atrophy

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 quantitative fluorescent polymererase chain reaction (QF-PCR) to detect aneuploidy of chromosomes 13,18,21, X and Y is offered, along with a follow up service via SNP Array testing or full karyotype for samples with abnormal scans or raised nuchal translucency. 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 (if not already undergoing SNP Array). Prenatal whole exome testing is also available for fetuses with multiple multisystem major structural and selected other abnormalities detected on ultrasound where a multidisciplinary review including the Clinical Genetics Service consider a monogenic malformation disorder is likely and molecular diagnosis may influence pregnancy or early neonatal management.

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.

Parental blood samples are no longer 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.

We offer Next Generation Sequencing panels including dosage analysis for hereditary breast and ovarian cancers panels and colorectal cancers panels (including Lynch syndrome and Polyposis). Predictive testing for at-risk relatives is also provided.

We offer Next Generation Sequencing panels (including dosage analysis where appropriate) for Cholestasis, Polycystic Liver disease, Intestinal failure, Wilson disease, Hirschsprung disease and Pancreatitis.

We offer next generation sequencing panels (including dosage analysis) for:

• Laterality disorders and isomerism
• Hereditary haemorrhagic telangiectasia (HHT)
• Pulmonary arterial hypertension
• Respiratory ciliopathies
• Pneumothorax
• Surfactant deficiency
• Pulmonary fibrosis