Referrals to the genetic clinic should be addressed to :-
Clinical Genetics Service
Level 2, Laboratory Medicine Building
Southern General Hospital
1345 Govan Road
Glasgow G51 4TF
Telephone enquiries are welcome, if you are uncertain of the need for a genetic consultation, or have other queries. Calls should be made, between 9am and 5pm,
to: 0141 354 9200 and will be directed to an available member of the medical staff.
It is helpful if you can include as much information as possible about relevant individuals in the referral letter. If possible, this should include individuals’ full name, with females’ maiden name, date of birth, and details of hospitals at which they have been treated.
Your patient will usually be allocated an appointment at the clinic closest to their home. Peripheral clinics may on occasion have longer waiting times. If your patient is willing to travel to Yorkhill to allow an earlier appointment please state this on the referral letter
What your Patient should expect at the Genetic Clinic
Common reasons for referral to the clinic include:-
Family History of cancer (40% of all referrals).
Learning Difficulties (10% of all referrals).
Single gene disorder in the family (25%) [e.g. cystic fibrosis (5%)].
Muscular dystrophies (3%).
Huntington disease (2%).
Child with congenital malformation or dysmorphic syndrome (12%).
Known chromosome abnormality in the family or interpretation of unusual or unexpected cytogentic prenatal diagnosis result (5%).
At the genetics clinic after taking a medical history, drawing a family tree, performing appropriate physical examination and ordering relevant tests, we aim to diagnose genetic disease as precisely as possible and may give information about:-
The nature of the diagnosis.
The chance of transmitting or developing genetic disease. Not infrequently, the diagnosis or likely inheritance mechanism cannot be exactly defined.In these circumstances, empirical risks or ‘best guess’ advice may be offered with families having to accept that lack of knowledge inevitably leads to uncertainty.
Prediction, prevention or avoidance through presymptomatic or prenatal tests.
Possibility of treatment or advisability of screening for complications.
Other options such as assisted conception techniques, if appropriate.
Information is given in a non-directive fashion so that families feel they may make informed decisions about, for example, having children, with or without or undergoing genetic tests.
Most patients subsequently receive a detailed letter outlining the clinic discussion, to retain for future reference.
Types of Genetic Tests
This form of testing involves directly identifying the mutation causing the disease in an individual.In this type of test the gene must have been cloned and the nature of the disease causing mutation known. In some diseases the common gene fault has been identified within the gene’s DNA sequence. It may be a simple matter to detect its presence e.g. the common cystic fibrosis gene mutation.
Common mutations present in unrelated affected individuals:-
In certain conditions such as sickle cell disease, haemochromatosis, fragile X syndrome, myotonic dystrophy, and Huntington’s Disease, the disease is caused, in the majority of cases, by one or a few mutations. The actual proportion of cases caused by one particular mutation may vary with the racial origin of the population studied. For example, 70% of CF mutations in the Scottish population are caused by one particular DNA sequence change, delta F508. Therefore, if a healthy Scottish individual is tested and found not to have this mutation, the chance that s/he carries a CF gene is decreased by 70%.
Knowledge of common mutations permits DNA based confirmation of diagnosis. Unlike genetic linkage studies (see below), there is no error from genetic recombination attached to testing.
In the UK, some antenatal clinics and general practitioners offer delta F508 CF carrier screening. However, population screening for genetic diseases or gene carrier status raises economic, ethical and moral issues.
"Private mutations” causing disease in single affected individuals:-
Many diseases are caused by a myriad of different mutations, each family having its own ‘private’ mutation. In these cases, the entire gene of an affected member of a family must be searched for the mutation and, depending on the size of the gene, this can be a very lengthy procedure or one which is presently impossible. Once identified, a private mutation can be looked for in asymptomatic members of the same family. For some conditions more than one gene may be involved and testing can be very complex (e.g retinitis pigmentosa, familial breast cancer)
Family Linkage Studies
This more rarely used technique involves indirectly assessing whether an individual has inherited a chromosome carrying a particular disease gene or the other copy of that chromosome which does not carry that gene mutation. An advantage of this test is that the disease gene in question does not need to have been isolated, although knowledge of its chromosomal location is vital. It can also occasionally be used to study conditions, like Marfan syndrome, where although the defective gene has been cloned, in a single affected individual it may be impossible to identify the precise gene fault and there is no DNA-based diagnostic test.
Fortunately, each individual’s DNA contains many harmless variations in its genetic sequence - these variations are the basis of paternity testing by the genetic fingerprinting technique. The technical name for non-disease causing genetic variation is polymorphism.
A polymorphic DNA marker, which lies next to, or within, the disease-causing gene, allows the chromosome with the mutation to be distinguished from the other one by virtue of its marker ‘type’.The disease linked marker is then ‘tracked’ in the family under study and its inheritance is shown to follow the inheritance of the gene causing the disease as it passes from one generation to the next.
Therefore, the requirements for linkage studies are:-
Knowledge of the disease gene’s chromosomal location.
Suitable polymorphic markers adjacent to the disease gene.
Relatives who are all willing to contribute DNA samples for comparison.
Absence of non-paternity within the family.
Markers able to distinguish the disease gene and its normal allele in consultands.
Low (< 5%) recombination rate between the marker and the abnormal gene
(Further information on any of the points above can be obtained from the Molecular Genetics Division section of this website)