Peking Union Medical College doctor says | How much do you know about screening for carriers of single gene genetic diseases?

Every couple of childbearing age is looking forward to having a healthy baby, but did you know that the total incidence of birth defects in China is about 5.6%. Based on the 16 million newborns each year, there will be 900,000 newborns with defects each year. Among the various causes of birth defects, single-gene genetic diseases account for about 22.2%. Studies have shown that on average, each normal person carries 2.8 pathogenic variant genes for recessive genetic diseases. The mutant genes can come from both parents and themselves, and may be inherited by the next generation. Carrier couples often do not have any symptoms, but are at risk of giving birth to children with recessive genetic diseases. In routine prenatal examinations, children with recessive genetic diseases usually cannot be detected as abnormal until symptoms appear after birth. So how can parents who are preparing for pregnancy or pregnant check the risk of giving birth to children with recessive genetic diseases in a timely manner? Don't worry, doctors from the Obstetrics Center of Peking Union Medical College Hospital are here to help you solve your problems——

Author: Hao Na

Chief Technician of Obstetrics Center, Peking Union Medical College Hospital

Audit expert: Jiang Yulin

Deputy Chief Physician, Obstetrics Center, Peking Union Medical College Hospital

What is a single gene disease?

Single gene genetic diseases refer to genetic diseases controlled by a pair of alleles, with more than 9,000 types, such as pseudohypertrophic muscular dystrophy, spinal muscular atrophy, thalassemia, phenylketonuria, etc. The comprehensive incidence of single gene diseases in the population is as high as 1%, among which the inheritance pattern of single gene recessive genetic diseases is as follows:

When a person carries a mutated gene for a single gene recessive genetic disease, we call it a carrier. The carrier himself will not get sick, but there is a 50% chance of passing the mutated gene to the child. When a couple are both carriers of the same single gene recessive genetic disease, and the fetus inherits the couple's defective genes at the same time, they will become ill in the future and become patients. Such a couple has a 25% chance of giving birth to a child with the genetic disease each time they become pregnant, and a 50% chance of giving birth to an asymptomatic carrier. In addition, when the woman is a carrier of the pathogenic gene for an X-linked recessive genetic disease, there is a 50% chance that the boy born in each pregnancy will be a child with the disease, and 50% of the girls born will be carriers.

What are the dangers of common single gene genetic diseases?

Single gene genetic diseases pose a great threat to the life and health of patients. Most single gene genetic diseases can cause death, serious malformation or disability, and there is a lack of targeted treatment methods and therapeutic drugs (only about 5%). The cost of treatment is expensive, and usually only symptomatic treatment or rehabilitation treatment can be adopted. Giving birth to a child with a serious single gene genetic disease brings enormous burden and trauma to the family and society. Therefore, for expectant parents, it is of great significance to conduct effective risk assessment and diagnosis and identification of common single gene genetic diseases during the preparation period or early pregnancy.

How to assess the reproductive risk of single gene genetic diseases?

Don't worry, expectant parents can perform carrier screening by blood tests during the preparation for pregnancy or early pregnancy, and test for common single-gene genetic diseases to check for pathogenic gene mutations. If the test finds that the couple is also a carrier of a single-gene genetic disease, it is necessary to combine genetic counseling, prenatal testing or diagnosis, assisted reproductive technology, etc. to effectively prevent the fetus from having serious single-gene genetic diseases, which is of great significance for reducing birth defects and improving the quality of the newborn population.

Who should be screened for single gene recessive genetic disease carriers?

Couples of childbearing age who intend to have children can undergo screening for single-gene recessive genetic disease carriers during the pregnancy preparation period or early pregnancy to understand their own mutant gene carrier status, detect fertility risks early and intervene in time, which can effectively prevent the occurrence of serious genetic diseases. International authoritative organizations have pointed out that it is necessary for every couple of childbearing age to conduct a genetic disease fertility risk assessment. Currently, many European and American countries have recommended that genetic disease carrier screening be included in routine testing during the pregnancy preparation period or early pregnancy.

Warm reminder : Patients who are highly suspected of having a single gene genetic disease, couples with a family history of genetic diseases, or couples who have given birth to children with genetic diseases, need to first undergo genetic diagnosis and screening for the causes of their own diseases or family history, and then the doctor will advise whether they are suitable for single gene disease carrier screening.

Single gene disease carriers

Best time to screen

The best time to conduct single gene genetic disease carrier screening is during the pregnancy preparation period. During this period, prospective parents have more time, so they can consider and make decisions based on the test results more easily, and there are more alternative solutions. Don't worry if you miss the pregnancy preparation period, you can also do screening in the early pregnancy, but the time is tight during this period, so it is recommended that both husband and wife have blood tests at the same time.

Screening for carriers of single-gene genetic diseases is simple and quick. Expectant parents first receive professional consultation in the outpatient clinic and sign the relevant informed consent form. Then both the couple will have blood drawn (3 to 5 ml of peripheral blood) for testing, and the results will generally be available in 3 to 4 weeks.

References:

[1]http://www.omim.org/statistics/entry

[2] http://www.who.int/

[3] ORPHAN DRUG REPORT 2014

[4] Bell CJ, Dinwiddie DL, Miller NA et al. Carrier testing for severe childhood recessive diseases by next-generation sequencing. Sci Transl Med. 2011 Jan 12;3(65):65ra4.

[5] http://www.ncbi.nih.gov/books

[6] Xu, et al. J Clin Pathol 2004,57:517-22.

[7] Xiong, et al. Clin Genet 2010, 78:139-48

[8] Gu Xuefan, ed. Clinical Genetic Metabolic Diseases, People’s Medical Publishing House, June 2015.

Content from: Dr. Hao Na from Union Medical College said