What are the common genetic conditions that Chinese individuals should be screened for?

Common Genetic Conditions for Chinese Individuals: Screening Recommendations

Chinese individuals should be screened for thalassemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and monogenic disorders with known pathogenic variants, as these represent the most prevalent genetic conditions in this population.

Thalassemia

Thalassemia is highly prevalent in southern China and represents a significant genetic condition requiring screening.

• Alpha-thalassemia mutations:

  • The --SEA deletion (65.12%)
  • -α3.7 deletion (19.05%)
  • -α4.2 deletion (8.05%)

• Beta-thalassemia mutations:

  • IVS-II-654(C→T) (40.39%)
  • CD41-42(-TCTT) (32.72%)
  • -28(A→G) (10.11%)
  • CD17(A→T) (9.32%)

Screening is particularly important for couples planning pregnancy, as thalassemia can lead to significant morbidity and mortality. According to guidelines, hematopoietic stem cell transplantation (HSCT) is a curative option for severe cases, with specific conditioning regimens recommended for Chinese patients 1.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

G6PD deficiency is endemic in Southern Chinese populations with an overall prevalence of 2.10% nationally 2.

• Most common G6PD mutations in Chinese populations:
  • G6PD Canton (c.1376 G→T) (33-46%)
  • G6PD Kaiping (c.1388 G→A) (30-39%)
  • G6PD Gaohe (c.95 A→G) (6-9%)
  • G6PD Chinese-5 (c.1024 C→T) (3-4%)

Universal screening for G6PD deficiency is already implemented for newborns in Hong Kong, Taiwan, and Singapore 3. This is critical as G6PD deficiency can lead to hemolytic anemia when exposed to certain medications, foods, or infections.

Monogenic Disorders

The Chinese Expert Consensus Guideline on Preimplantation Genetic Testing recommends screening for monogenic disorders in specific circumstances 1:

• When one family member has a known monogenic disorder
• When both partners are carriers of the same monogenic disorder
• When the couple has conceived or is at high risk of conceiving a child with a monogenic disorder that results in death, malformation, or disability

Genetic Conditions in Specific Populations

Diabetes-Related Genetic Conditions

• Monogenic diabetes: Should be considered in patients with:
  • Diabetes diagnosed in the first 6 months of life (neonatal diabetes)
  • Atypical presentation not consistent with type 1 or type 2 diabetes
  • Family history suggesting autosomal dominant inheritance (MODY) 1

Cancer-Related Genetic Conditions

In Chinese lung cancer patients, specific germline mutations have been identified that may warrant screening in high-risk families:

• EGFR germline mutations (0.2% prevalence)
• ERBB2, CHEK2, and other germline mutations associated with increased cancer risk 1

Screening Approach

1. Thalassemia screening:

   • Complete blood count with red cell indices
   • Hemoglobin electrophoresis
   • Molecular genetic testing for common mutations based on initial screening results

2. G6PD deficiency screening:

   • Quantitative enzyme level screening
   • Genetic testing for common mutations if enzyme levels are low or borderline
   • Repeat testing after any hematopoietic stem cell transplantation 3

3. Monogenic disorder screening:

   • Targeted genetic testing based on family history
   • Preimplantation genetic testing for couples with known genetic risks
   • Whole exome or genome sequencing for undiagnosed conditions with strong genetic suspicion

Important Considerations

• The prevalence of genetic conditions varies significantly across different regions of China, with southern provinces showing higher rates of thalassemia and G6PD deficiency 4, 5.
• Female carriers of X-linked conditions like G6PD deficiency may have variable clinical presentations due to X-chromosome inactivation patterns.
• Genetic counseling is essential before and after genetic testing to ensure proper understanding of results and implications for family planning.

By implementing comprehensive screening for these common genetic conditions, significant morbidity and mortality can be prevented through early intervention, appropriate management, and informed reproductive decisions.