Heredity

Patient's question:

I have a hereditary disease called neurogenic muscular atrophy. I would like to ask the doctor what the probability of inheritance is for this disease, what its symptoms are, and how I can get a physical examination to check if I have been inherited the disease. How much might the cost be? Now my wife is pregnant, and I am very scared. My grandfather, my older uncle, and my younger uncle all have this disease. My father and my younger brother are healthy. I hope the doctor can provide information. Thank you very much.
First follow-up question: (2007-8-6 14:00:13) What are the symptoms of this disease, how can it be checked, and what might the cost be?

Doctor's answer:

Is there a risk associated with genetic testing?
Yes. In recent years, you may have often heard people talk about genetic testing, not only in MDA healthcare facilities but also in other healthcare facilities, as well as in newspapers and on television. With the advancement of technology, more and more genes have been found to be associated with certain diseases, including tumors, heart disease, and even rare metabolic and muscle diseases.
Privacy is a matter of genuine concern. Some people are very worried that genetic testing may reveal their privacy and affect their ability to purchase insurance or find employment. These concerns are not entirely unfounded.
The law is unclear about protecting individuals from discrimination based on insurance and employment due to genetic testing. Regulations vary by state, and even routine privacy protections can be difficult to guarantee.
You can reduce the risk by choosing a reputable genetic counselor and informing them of your privacy concerns. In some cases, you may also choose not to undergo genetic testing.
Like all other tests, genetic testing can sometimes be inaccurate. Good laboratory results are more accurate, but errors can still occur. Sometimes, interpreting the results can be challenging.
For example, a test may detect a mutation in a gene, but the significance of that mutation may not be clear. Experts may not know what the consequences of a previously undiscovered mutation will be, and in fact, not all gene mutations are harmful.
Prenatal genetic testing is a type of predictive genetic testing that targets a fetus in the uterus or an embryo created through in vitro fertilization.
If prenatal testing reveals that a fetus may have a genetic disease, parents often find it difficult to make decisions. In such cases, genetic counseling, as well as psychological and emotional support, may be helpful.
There is no consensus on whether children should undergo genetic testing for a gene mutation before symptoms appear or be tested to determine if they are carriers. Many institutions strongly oppose genetic testing of children, and some healthcare facilities prohibit it unless there are compelling reasons (e.g., effective treatments available before symptoms manifest).
Medical experts believe that testing children for genetic diseases or carrier status has more disadvantages than advantages. It is better to let them make the decision themselves when they are adults. Genetic testing is a relatively new technology, and the legal, ethical, and medical issues surrounding it are far from being fully understood. At the same time, parents may prefer to wait until their children are older to make such decisions. Further consultation with genetic experts is necessary.
For asymptomatic individuals who may develop a disease in the future or carriers (both adults), genetic testing can sometimes lead to unexpected issues. Testing adults who already show symptoms or have a family history of genetic diseases is generally the least controversial. However, this can also lead to unforeseen problems, such as a test result suggesting that other family members may have a genetic disease. Whether to inform potentially affected family members is a complex issue.
Test results can also be a source of mental stress for the individual, causing anxiety and depression, especially when there are no treatment options available or when they are planning to start a family.
If a test reveals that a genetic disease is inherited from either parent, it may strain the relationship between the parents or even lead to criminal behavior toward the carrier. In such cases, consultation with a geneticist or other experts is necessary.
Can genetic diagrams predict the occurrence of genetic diseases in a family?
No. Many people have seen diagrams of genetic inheritance patterns in school or hospitals, but unfortunately, these diagrams can lead to misunderstandings.
Genetic diagrams show the theoretical probability of a child having a disease with each pregnancy.
This is like flipping a coin. Each flip has a 50% chance of landing heads and a 50% chance of landing tails.
In reality, if you flip a coin six times, you might get a variety of combinations: all six heads, five heads and one tail, four heads and two tails, and so on.
Each flip is an independent probability—50% heads and 50% tails. The result of the second flip is not affected by the first, the third is not affected by the first two, and the sixth is not affected by the first five.
This is similar to having children. The probability of a parent passing on a particular gene to a child is always 50%, regardless of how many children they have. Each pregnancy has the same probability.
Don’t assume that if one child in a genetic diagram is affected and the other is not, you will have two affected and two unaffected children if you have four.
Just as flipping a coin six times and getting six heads in a row can happen, you could have six affected children if you have six.
What is the reality of genetic diseases in families?
In real life, it is impossible to predict whether a particular gene will be passed on to a child during pregnancy, just as it is impossible to predict which side of a coin will land face up with each flip. Even if the probability of heads and tails is 50%, you could still flip a coin six times and get six heads.
This manual provides several examples of genetic diseases occurring in families. These diagrams are called pedigree analyses. Geneticists or genetic counselors can create a pedigree diagram based on your description, and you may also see such diagrams in books or online.
Can a disease that has never appeared in a family be genetic?
This is a common question asked by individuals diagnosed with genetic diseases or parents who have had children with genetic diseases. They say, "No one in our family has ever had this disease. How can it be genetic?" Their confusion is understandable.
This situation is very common—genetic diseases can appear in families where they have never been seen before.
One factor or cause of this is autosomal recessive inheritance. In this type of genetic disease, both copies of the gene on the same chromosome must mutate for the disease to manifest. One mutated gene may have been present in the family for several generations. Since it is a recessive gene, individuals with only one mutation do not show symptoms. The disease only manifests when a child inherits a mutated gene from another family member.
A similar mechanism occurs in X-linked inheritance. In a family, a female may carry a mutated gene, but since only one copy of the gene on the X chromosome is mutated, she does not show symptoms of the disease. The disease only becomes apparent when the mutated X chromosome is passed to a male child. Generally, female carriers of X-linked genetic diseases rarely show obvious symptoms.
Another scenario where a dominant or X-linked genetic disease appears in a family where it has never been seen before is when one or more sperm or egg cells from the father or mother undergo a gene mutation. Since routine tests, including DNA tests, are based on blood samples, such mutations cannot be detected. If such a mutated sperm or egg develops into a child, the child will be affected. This is not uncommon.
If both parents are not genetic disease carriers and have been tested to confirm they are not, but they have a child with a genetic disease, some parents may believe it was a one-time event caused by a mutation in a sperm or egg. They think such an event will not happen again.
Unfortunately, this view has been proven wrong, especially in cases of Duchenne muscular dystrophy. Now, it has been understood that sometimes multiple eggs in a mother’s body may carry mutated genes, a condition that cannot be detected through routine blood tests. Such mothers may have multiple affected children, all of whom are developed from egg cells containing mutated genes.
In a sense, such mothers are also carriers, but the mutated genes are present in some of their cells rather than in all of them. They can be considered "partial carriers" or "mosaic carriers." For them, predicting genetic risk is very difficult.
Other inherited neuromuscular diseases may have similar situations, though they have not been studied as extensively as Duchenne muscular dystrophy. For example, in dominant genetic diseases, one or more children may inherit a mutated gene from a mosaic carrier parent and develop the disease. For recessive genetic diseases, a child may inherit one mutated gene from one parent (a "complete carrier") and another mutated gene from the other parent (a "mosaic carrier"). Routine tests cannot detect mosaic carriers in parents.
Recent research provides the most important information: for parents who have had children with genetic diseases, a normal (non-carrier) blood test result is unreliable. Gene mutations may not be present in blood cells but in sperm or egg cells. If multiple such cells contain gene mutations, subsequent children may still develop the same genetic disease.
If you have already had a child with a genetic disease, you can consult with a genetic expert to help you decide about future pregnancies. The risk of having an affected child varies depending on the specific genetic disease.
Are there genes outside the nucleus?
Yes. In addition to genes in the nucleus, there are also genes outside the nucleus in human cells. Most human genes are located on chromosomes within the nucleus, which are the genes we have discussed earlier.
Another type of gene accounts for less than 1% of the total human gene pool. These are mitochondrial genes, which are found on circular chromosomes within mitochondria. Mitochondria are the "energy factories" of cells.
What is the function of mitochondrial genes?
Mitochondria contain about 37 genes, most of which are related to energy production in cells. Scientists believe that mitochondria were once independent organisms, similar to bacteria, and that they retained their own genes after becoming components of animal cells. These genes are located on circular chromosomes and encode 13 types of proteins, all of which are necessary for normal mitochondrial function. These genes also encode 24 types of special RNA molecules, which are components required for protein synthesis in mitochondria. It is worth noting that some proteins in mitochondria are encoded by nuclear genes and are synthesized outside the mitochondria before being transported to them.
Can mutations in mitochondrial genes cause genetic diseases?
Yes, mutations in mitochondrial genes can cause genetic diseases. It can be imagined that mutations in mitochondrial genes may lead to energy production failures in cells, causing diseases in energy-intensive cells such as nerves and muscles. These diseases are collectively called mitochondrial diseases, and the muscle diseases involved are called mitochondrial myopathies.
How are mitochondrial gene mutations inherited?
Current research suggests that sperm mitochondria are cleared by the egg during fertilization, and the mitochondria of the embryo come from the mother’s egg rather than the father’s sperm. Therefore, the inheritance of mitochondrial gene mutations is very different from the inheritance of nuclear genes. Autosomal dominant, recessive, and X-linked inheritance patterns do not apply here.
Having some mitochondria with mutated genes is a normal phenomenon and generally does not cause serious problems (some believe that aging is caused by the accumulation of too many gene mutations in mitochondria). Normal mitochondria can usually provide enough energy for the body to use. However, when the proportion of mutated mitochondria exceeds a certain threshold (around 30%), energy deficiency becomes severe, leading to mitochondrial diseases.
Mothers pass on mitochondrial mutations to their children, while fathers do not, a phenomenon called maternal inheritance. The severity of the disease in the child depends on the proportion of mutated mitochondria passed down by the mother.
Mutations in mitochondrial DNA can also occur during embryonic development. Not all mitochondrial mutations are inherited; some occur in embryos developing in the uterus.
Researchers have found that mitochondrial gene mutations often occur after sperm and egg cells combine to form an embryo. Based on current observations, these mutations are not inherited.
Does nuclear DNA affect mitochondria?
Yes. Nuclear DNA also affects mitochondrial function, so some mitochondrial diseases follow inheritance patterns similar to other typical genetic diseases.
Most proteins in mitochondria are not synthesized within them but are encoded by nuclear DNA and synthesized outside the mitochondria. After synthesis outside the mitochondria, these proteins enter the mitochondria and participate in energy production.
You must imagine that nuclear gene mutations can affect mitochondrial function, which is another factor or cause of mitochondrial diseases. This is not caused by mitochondrial DNA mutations. The inheritance patterns of nuclear genes that cause mitochondrial diseases are the same as autosomal and X-linked inheritance.
When planning a family, it is very important to determine whether mitochondrial diseases in the family are caused by mitochondrial DNA mutations or nuclear DNA mutations. These two types of mutations have different inheritance patterns and different impacts on the family.
MDA’s Goals and Research Programs
The Muscular Dystrophy Association (MDA) fights against neuromuscular diseases through global, non-parallel research, nationwide healthcare service programs, extensive professional training, and public health education. MDA funds 400 research projects in the U.S. and around the world, all aimed at deepening the understanding of neuromuscular diseases and developing treatments for muscular dystrophy and related conditions. MDA’s expert committees review these research projects. MDA operates 230 healthcare facilities to provide comprehensive care for children and adults with neuromuscular diseases. MDA’s research projects cover some of the following diseases:
References: Muscular Dystrophies