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• A number of genetic conditions are more common amongst descendants of Central and Eastern European (Ashkenazi) Jews than in people from other population groups. These conditions include Tay-Sachs disease, Canavan disease, Fanconi anaemia, familial dysautonomia and cystic fibrosis (CF)
• All of these are genetic conditions due to inheriting two faulty copies of a gene
• Tay-Sachs disease (TSD) is a degenerative condition of the nervous system where apparently healthy babies at about 6 months of age lose already acquired skills, gradually become blind, paralysed and unaware of his/her surroundings and die before about 5 years of age. All have a 'cherry-red spot' on the retina at the back of the eye even before symptoms appear and both boys and girls are affected
• TSD is due to inheriting two faulty copies of a gene called the HEX A gene that contains the information for the production of an important protein in the brain and nervous system
• People who have one working copy of the HEX A gene and one that is faulty are called 'carriers' of the change that makes the gene faulty ie. genetic carriers for TSD
• Genetic carriers for TSD do not have Tay-Sachs disease because they can still produce enough HEX A protein
  • About 1 in 25 Ashkenazi Jewish Australians are genetic carriers for TSD
• People with TSD have both copies of their HEX Agene faulty: they cannot produce the important HEX A protein
• The pattern of inheritance in families of the faulty gene causing TSD is described as autosomal recessive inheritance
• When both parents are carriers of the faulty gene, they have 1 chance in 4 (or 25% chance) in every pregnancy of having a child with TSD
• If only one parent is a carrier of the faulty gene, they will not have a child with TSD
• The information above applies similarly to the inheritance pattern of Canavan disease, Fanconi anaemia, familial dysautonomia and CF
• Genetic testing to determine if a person is a carrier of the faulty gene(s) involved in these conditions can be discussed with a doctor or a genetic counsellor. Testing may be available pre-pregnancy and in pregnancy and is appropriate when there is a family history or a blood relative is a genetic carrier for these conditions
• Where both parents are genetic carriers of the same genetic condition, they can find out information about the condition and their chance of having an affected child and discuss their reproductive options with a genetic counsellor (see Genetics Fact Sheet 3)
• Genetic carrier screening may also be available for these conditions based on Ashkenazi Jewish ancestry, even if there is no family history of the condition. The screening conducted pre-pregnancy, including with senior high school students as part of a community genetics screening program and in pregnancy will only pick up those who are carriers of one of the more common changes in the gene(s) involved (see Genetics Fact Sheet 21)

Tay-Sachs disease (TSD) is a severe genetic condition of the nervous system and is named after two doctors - a physician, Dr Bernard Sachs and an ophthalmologist, Dr Warren Tay - who first described the condition in 1887. They noted that a number of children of Central and Eastern European (Ashkenazi) Jewish ancestry:

• At birth had no apparent problems
• By about 6 months stopped smiling, crawling or turning over, lost their ability to grasp or reach out, and gradually became blind, paralysed and unaware of their surroundings despite seeming otherwise happy and healthy from birth
• All had a 'cherry-red spot' on the retina at the back of the eye even before symptoms appeared (see Figure 35.1)
• Both boys and girls were affected and death occurred before the age of 5

Figure 35.1: The 'cherry red spot' seen on the retina at the back of the eye
is diagnostic for Tay-Sachs disease even before other symptoms are evident.
(Photo William F Hoyt)

An enzyme is a protein that is essential for normal body function. Everyone has a particular enzyme called hexosaminidase A or HEX A that breaks down a fatty substance found in the brain called GN12 ganglioside. Small amounts of this substance are essential for proper brain function.

Babies born with TSD do not produce the HEX A enzyme and so the fatty substance accumulates in their brain cells, irreversibly damaging the cells.

TSD is a genetic condition (see Genetics Fact Sheet 2). Therefore it is passed from parents to children in their genes.

Two factors influence the pattern of inheritance of the faulty HEX A gene causing TSD in families.

1. The HEX A gene is located on chromosome 15, an autosome (one of the numbered chromosomes)
2. The effect of the change in the gene is 'recessive' or hidden by the presence of the working copy of the gene (see Genetics Fact Sheets 1, 4 & 5)

The pattern of inheritance in families of the faulty gene causing TSD is therefore described as autosomal recessive inheritance (see Genetics Fact Sheet 8).

In Figures 35.2 and35.3 which illustrate the pattern of inheritance, the faulty HEX A gene is represented by 'r'; the working copy by 'R'. There are four possibilities, in every pregnancy, for the combinations of genes passed from the parents.

As shown in Figure 35.2, if a couple are both carriers of the faulty HEX A gene, in every pregnancy there is a

• 1 in 4 chance, or 25%, that they will have a child who inherits both copies of the faulty gene from his/her parents. In this case, no working gene product will be produced and their child will be affected by TSD
• 1 in 4 chance, or 25%, that their child will inherit both copies of the working gene and will be unaffected by TSD and cannot pass the faulty gene on to their children
• 1 in 2 chance (2 in 4 chances), or 50%, that their child will inherit one faulty copy of the gene and one working copy of the gene from each parent and he/she will be an unaffected genetic carrier for TSD, just like the parents

Figure 35.2: Autosomal recessive inheritance where both parents are carriers of the faulty
HEX A gene. The faulty HEX A gene copy is represented by 'r'; the working copy by 'R'.

Figure 35.3: Autosomal recessive inheritance where only one parent is a carrier of the faulty
HEX A gene. The faulty HEX A gene copy is represented by 'r'; the working copy by 'R'.

If only one parent is a carrier of the faulty HEX A gene (Figure 35.3), in every pregnancy there is

• No chance that the couple will have a baby affected with TSD
• 1 chance in 2 (2 chances in 4) or 50% that the baby will be an unaffected genetic carrier for TSD, just like his/her parents

If both partners in a couple are genetic carriers for these conditions, they can find out information about the condition and their chance of having an affected child and discuss their reproductive options with a genetic counsellor (see Genetics Fact Sheet 3)

Prenatal testing for these conditions in pregnancy and in association with assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) may be possible (see Genetics Fact Sheets 17C & 18)

Other Genetics Fact Sheets referred to in this Fact Sheet: 1, 2, 3, 4, 5, 8, 17C, 18, 21, 33

Barlow-Stewart K, Burnett L, Proos A, Howell V, Huq F, Lazarus R and Aizenberg H. (2003). A genetic screening programme for Tay-Sachs disease and Cystic Fibrosis for Australian Jewish high school students. Journal of Medical Genetics 40: e45 [online]. Available from: http://www.jmedgenet.com/cgi/content/full/40/4/ed45. [Accessed June 2007]

Kaback MM, Lim-Steele J, Dabholkar D, Brown D, Levy N and Zeiger K. (1993). Tay-Sachs disease - carrier screening, prenatal diagnosis and the molecular era, an international perspective, 1970 to 1993. JAMA 270:2307-15

Kaplan F. (1998). Tay-Sachs disease carrier screening: a model for prevention of genetic disease. Genet Test 2:271-92

Online Mendelian Inheritance in Man, OMIM. McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD) [online]. Available from: http://www.ncbi.nlm.nih.gov/omim/. [Accessed June 2007]