Challenging the dogma of the healthy heterozygote: Implications for newborn screening policies and practices.
Mol Genet Metab
; 134(1-2): 8-19, 2021.
Article
in En
| MEDLINE
| ID: mdl-34483044
ABSTRACT
Heterozygous (carrier) status for an autosomal recessive condition is traditionally considered to lack significance for an individual's health, but this assumption has been challenged by a growing body of evidence. Carriers of several autosomal recessive disorders and some X-linked diseases are potentially at risk for the pathology manifest in homozygotes. This minireview provides an overview of the literature regarding health risks to carriers of two common autosomal recessive conditions on the Recommended Uniform Screening Panel sickle cell disease [sickle cell trait (SCT)] and cystic fibrosis (CF). We also consider and comment on bioethical and policy implications for newborn blood screening (NBS). Health risks for heterozygotes, while relatively low for individuals, are often influenced by intrinsic (e.g., other genomic variants or co-morbidities) and extrinsic (environmental) factors, which present opportunities for personalized genomic medicine and risk counseling. They create a special challenge, however, for developing screening/follow-up policies and for genetic counseling, particularly after identification and reporting of heterozygote status through NBS. Although more research is needed, this minireview of the SCT and CF literature to date leads us to propose that blanket terms such as "healthy heterozygotes" or "unaffected carriers" should be superseded in communications about NBS results, in favor of a more nuanced paradigm of setting expectations for health outcomes with "genotype-to-risk." In the molecular era of NBS, it remains clear that public health needs to become better prepared for the full range of applied genetics.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neonatal Screening
/
Heterozygote
/
Genetic Carrier Screening
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Aspects:
Ethics
Limits:
Humans
/
Newborn
Language:
En
Journal:
Mol Genet Metab
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
METABOLISMO
Year:
2021
Document type:
Article