Rare! Mothers routinely poor genetic tests are normal, but they give birth to severely poor children

Text/Yangcheng Evening News all-media reporter Zhang Hua

Correspondents Liu Yuanling, Cai Jiaqi, Gu Heng

Photo/Courtesy of respondents

The parents' routine thalassemia (hereinafter referred to as the ground poverty) genetic test is normal, but the 4-year-old daughter and 3-year-old son born are severely poor! This is extremely rare. It turned out that the couple had passed on the rare genes of the land poverty to the children, thus giving birth to severe poverty.

May 8 is World Poverty Day, and Guangdong is one of the highest incidence areas of thalassemia, with an average of 1 in 6 people carrying the poverty gene. Guangdong Provincial Maternal and Child Health Hospital is responsible for the province's poverty screening, the project leader Wang Xionghu introduced to reporters, Guangdong Province last year free poverty screening more than 1.2 million couples of childbearing age, more than 280,000 pairs of re-screening, more than 100,000 pairs of genetic testing, more than 6,700 cases of prenatal diagnosis, found more than 1,100 cases of severe poor fetuses, all of which carried out early prenatal intervention, the prevention and control effect is obvious.

Some medical institutions in the province can conduct free screening for local poverty

The mother's routine genotype was normal, but she gave birth to two severely poor children

What is the inheritance of rare poor genes? Zheng Lixin, chief expert of eugenic genetics at Guangdong Reproductive Hospital, introduced that Sun Ming (pseudonym) and his wife are from Zhaoqing, Guangdong Province, and after giving birth to their eldest daughter in early 2018, the younger son was born again in 2019. However, from 2020 onwards, the mother of the child found that the two-year-old daughter's abdomen was getting bigger and bigger, her face was pale, and she was significantly shorter and thinner than children of the same age. So the couple took the child to the local hospital to see a doctor, and the doctor found that his eldest daughter had a large liver and spleen and had severe anemia. At the same time, it was found that the younger son also had anemia. Local doctors suspect both children have severe thalassemia.

"The doctor said that both children had severe anemia and had to be transfused once a month." Upon hearing the news, the couple was confused, knowing that the child was about to face the treatment dilemma, and the child's mother could not cry.

"After testing for mutations in the common ground poverty gene, my two children and I carry the βIVS-II.-654 pathogenic gene, and my wife has a normal genotype." Sun Ming said, "This is strange, only two homogenic carriers have a 1/4 chance of having children with severe poverty, while my wife does not, why are my two children severely poor?" ”

Genetic patterns of conventional thalassemia

Children inherit genes that are rarely poor in their parents

Therefore, Sun Ming and his wife brought their two children to guangdong reproductive hospital for treatment. At that time, the hospital could provide free genetic testing services for patients with rare poverty. Zheng Lixin said: "We observed that the two children had obvious land poverty, and after checking the results of the outer hospital examination, we felt that the phenotype and genotype did not match. Considering that it may be a rare poverty, a comprehensive genetic test for the family was carried out free of charge. ”

Unsurprisingly, Sun Ming's wife was found to carry the ααanti 3.7 gene after genetic sequencing. The two children were also carrying βIVS-II.-654 composite αααanti 3.7. "Here's the problem." Professor Zheng Lixin said, "There are some couples, one of the two parties is α poor carrying, one is β poor carrying, the offspring may be a double heterozygous (light ground poverty) that α merged with β, because the α and β globin chains are reduced at the same time, the proportion is not out of balance, and generally does not lead to the occurrence of severe poverty." The special feature of this family is that the woman carries the ααanti 3.7 gene and the man's βIVS-II.-654 gene are inherited to the child, that is to say, the two children have 5 α genes to control α the production of the globin chain, 1 β gene to control the production β of the globin chain, and the ratio of α gene to the β gene is 5:1, which makes the α chain and the β chain extremely unbalanced, the morphology and structure of red blood cells are greatly affected, the deformation ability is poor, the survival time is short, and it is easy to destroy the hemolysis in the blood vessels. This can lead to severe clinical symptoms. That's the real reason. ”

Most patients with moderate to severe poverty rely on blood transfusions to sustain themselves

In the mainland, Guangxi, Guangdong and Hainan have the highest incidence of poverty. According to statistics in 2016, the gene carrying rate of the household registration population in Guangdong Province is about 16.8%, with an average of 1 carrier per 6 people.

How much of an impact does this high-prevalence genetic disorder have on health? Zheng Lixin said that the land poverty is mainly divided into α land poverty and β land poverty. Due to the different symptoms, the ground poverty can be divided into static type, light type, intermediate type and heavy type. Mild patients (also known as carriers of thalassemia) have no symptoms, are not harmful to their health, and are not detected until they are screened. Patients with moderate to severe disease have symptoms of anemia, gray face, fatigue, slow development, liver and spleen enlargement, and most rely on blood transfusions to maintain life. There are some severe case types that cause fetal edema, often with fetal stillbirth intrauterine or postnatal death.

Unfortunately, there are currently no drugs and mature gene therapy methods for local poverty, quiescent and mild poverty do not require special treatment, and patients with moderate and severe poor need regular blood transfusions and iron removal therapy to maintain life. According to the survey report on the prevention and treatment of thalassemia in China (2015), there are 300,000 patients with severe and intermediate poverty in the mainland, and up to 30 million people are carriers of the poor gene, and the prevention and treatment situation is very grim. There are two options for the treatment of poor patients, one is blood transfusion substitution treatment, that is, lifelong blood transfusion and use of iron remover, the average annual treatment cost is as high as 100,000 yuan or more; the other is transplant treatment (hematopoietic stem cell transplantation, umbilical cord blood transplantation), which is currently the only way to eradicate local poverty, with an average medical cost of 400,000 yuan.

Diversion hybridization is performed for soil poverty gene detection

Free screening throughout the province, early prenatal intervention

Carrying out premarital, pre-pregnancy and prenatal eugenic examinations in areas with high incidence of local poverty, and preventing the birth of severe poor children through medical interventions, are currently internationally recognized as the primary measures and important strategies for effective prevention and control of local poverty. In the past 10 years, Guangdong Province has carried out free routine initial screening for anemia for more than 18.18 million people, more than 1.15 million people have undergone genetic testing for local poverty, and more than 41,000 people have undergone free prenatal diagnosis, and 7176 cases of severe local poverty have been found, and 6753 cases of prenatal intervention have been carried out.

Although initial results have been achieved, the work of poverty prevention and control still has a long way to go. Guangdong Provincial Maternal and Child Health Hospital is responsible for the province's poverty screening, the project leader Wang Xionghu introduced to reporters, Guangdong Province last year free poverty screening more than 1.2 million couples of childbearing age, more than 280,000 pairs of re-screening, more than 100,000 pairs of genetic testing, more than 6,700 cases of prenatal diagnosis, found more than 1,100 cases of severe poor fetuses, all of which carried out early prenatal intervention, the prevention and control effect is remarkable.

If necessary, more comprehensive genetic testing for poverty should be carried out to warn of the existence of rare poverty

According to statistics, in the past two years, about 2,000 couples have gone to The Fertility Hospital in Guangdong Province for genetic screening of local poverty. Zheng Lixin reminded the public that if both couples carry the same type of thalassemia gene, the woman must undergo villous testing, amniocentesis or cord blood after pregnancy to obtain the fetal cell line gene analysis.

In addition, experts also pointed out that in addition to routine testing, more comprehensive genetic testing for poverty should be carried out when necessary, and the existence of rare poverty should be vigilant. For example, after giving birth to the first child in the above case, the child has symptoms and signs related to local poverty, and should go to the hospital in time for further investigation and timely discover abnormal gene carrying, so as to better guide prenatal diagnosis and avoid the risk of having another severely poor child. (For more news, please pay attention to Yangcheng Pie pai.ycwb.com)

Source | Yangcheng Evening News Yangcheng Pie

Editor-in-charge | Wang Moyi

Proofreading | Li Hongyu