Whole-genome sequencing could help lower infant mortality rates

What is the percentage of infant deaths caused by genetic diseases?

According to a study published in JAMA Network:

41% of infant deaths were caused by single-gene diseases.

For 30% of these genetic diseases, treatments were available.

Whole-genome sequencing can increase neonatal diagnosis of genetic diseases.

Early diagnosis enables immediate treatment to decrease infant mortality rates.

Article 1: Landscape of pathogenic mutations in premature ovarian insufficiency

This study identified pathogenic gene variants associated with premature ovarian insufficiency (POI), a major cause of female infertility affecting almost 4% of women under 40. POI happens when a woman’s ovaries stop working properly. It is highly heterogeneous and can be caused by genetic defects, autoimmune diseases, infections, or other factors. However, in many cases the cause is unknown. The researchers performed whole-exome sequencing in 1,030 patients with POI, uncovering hundreds of pathogenic and likely pathogenic variants in 23.5% of the patients. The findings could potentially improve the utility of diagnostic genetic screenings for POI. Read the full article here.

In summary: Pathogenic variants for a major cause of female infertility identified

Article 2: Reclassification of the etiology of infant mortality with whole-genome sequencing

Treatable genetic diseases cause more newborn deaths than currently thought. Rapid diagnostic whole-genome sequencing (WGS) could help lower infant mortality rates. The researchers studied 546 infants who underwent diagnostic WGS. Of this total, 112 died and 434 had an acute illness but survived. Single-gene diseases, including many treatable ones, were the most common identifiable cause of mortality in the newborns who died, occurring in 46 of the infants. These findings highlight the potential benefits of increasing neonatal diagnosis of genetic diseases and immediately implementing treatment to decrease infant mortality rates. Read the full article here.

In summary: Whole-genome sequencing can help lower infant mortality rates by improving neonatal diagnosis

Article 3: Circulating tumor DNA is prognostic in intermediate-risk rhabdomyosarcoma: a report from the children’s oncology group

This study suggests that analyzing circulating tumor DNA (ctDNA) in children with rhabdomyosarcoma, a rare adolescent soft tissue sarcoma, could help guide treatment. Rhabdomyosarcoma has two genetic subtypes, fusion-positive and fusion-negative, and half of the patients are diagnosed with intermediate-risk disease. Identifying patients who should enroll in clinical trials for a high-risk disease is crucial because survival after relapse is rare. The researchers found that ctDNA detection in these patients is significantly associated with a shorter event-free and overall survival, which could help refine prognoses. They also found that ctDNA was independently associated with outcomes in patients with fusion-negative rhabdomyosarcoma. The findings suggest that ctDNA will be an essential tool for future risk-stratified treatment strategies in rhabdomyosarcoma. Read the full article here.

In summary: Circulating tumor DNA as potential biomarker in rare childhood cancer

Article 4: The developmental basis of fingerprint pattern formation and variation

This recent study explains how fingerprints are formed and identifies the genes responsible. The researchers discovered that fingerprints start out looking similar to hair follicles and recruit cells from layers below the epithelium. However, slight differences in gene expression prevent the recruitment step, leading to the formation of a Turing pattern. This pattern, named after mathematician Alan Turing, forms stripes or spots in the presence of an activator and an inhibitor. In fingerprints, WNT and EDAR proteins act as activators that create ridges, while BMP proteins act as inhibitors. The Turing pattern starts in three areas in humans and matures into the unique fingerprint pattern each person is born with. The study’s findings on Turing patterns can also help explain other biological patterns such as zebra stripes and leopard spots. Read the full article here.

In summary: Genetic basis of fingerprints uncovered

New in Genetics issue February 2023. Every month, Medicover Genetics curates the most important peer-reviewed scientific publications related to genetics.

References

[1] Ke H et al. Landscape of pathogenic mutations in premature ovarian insufficiency. Nat Med. 2023 Feb;29(2):483-492. doi: 10.1038/s41591-022-02194-3. Epub 2023 Feb 2. PMID: 36732629; PMCID: PMC9941050. https://www.nature.com/articles/s41591-022-02194-3

[2] Owen MJ et al. Reclassification of the Etiology of Infant Mortality With Whole-Genome Sequencing. JAMA Netw Open. 2023 Feb 1;6(2):e2254069. doi: 10.1001/jamanetworkopen.2022.54069. PMID: 36757698; PMCID: PMC9912130. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2801195

[3] Abbou S et al. Circulating Tumor DNA Is Prognostic in Intermediate-Risk Rhabdomyosarcoma: A Report From the Children’s Oncology Group. J Clin Oncol. 2023 Feb 1:JCO2200409. doi: 10.1200/JCO.22.00409. Epub ahead of print. PMID: 36724417. https://ascopubs.org/doi/10.1200/JCO.22.00409

[4] Glover JD et al. The developmental basis of fingerprint pattern formation and variation. Cell. 2023 Feb 7:S0092-8674(23)00045-4. doi: 10.1016/j.cell.2023.01.015. Epub ahead of print. PMID: 36764291. https://www.cell.com/cell/fulltext/S0092-8674(23)00045-4