Editing Missense mutation (section)

=== Newborn Screening (NBS) ===
[[Newborn screening]] (NBS) for missense mutations is increasingly incorporating genomic technologies in addition to traditional biochemical methods to improve the detection of genetic disorders early in life. Traditional NBS primarily relies on biochemical assays, such as [[tandem mass spectrometry]],<ref>{{Cite journal |last=Levy |first=Harvey L |date=1998-12-01 |title=Newborn Screening by Tandem Mass Spectrometry: A New Era |url=https://academic.oup.com/clinchem/article/44/12/2401/5643158 |journal=Clinical Chemistry |language=en |volume=44 |issue=12 |pages=2401–2402 |doi=10.1093/clinchem/44.12.2401 |pmid=9836702 |issn=0009-9147}}</ref> to detect metabolic abnormalities indicative of conditions like [[phenylketonuria]] or [[congenital hypothyroidism]].<ref>{{Cite journal |last=Cunningham |first=George |date=2002-04-04 |title=The Science and Politics of Screening Newborns |url=http://www.nejm.org/doi/abs/10.1056/NEJM200204043461411 |journal=New England Journal of Medicine |language=en |volume=346 |issue=14 |pages=1084–1085 |doi=10.1056/NEJM200204043461411 |pmid=11932477 |issn=0028-4793|url-access=subscription }}</ref> However, these methods may miss genetic causes or produce ambiguous results. To address these deficiencies, [[next-generation sequencing]] (NGS) is being added to NBS programs.<ref>{{Cite journal |last1=Remec |first1=Ziga I. |last2=Trebusak Podkrajsek |first2=Katarina |last3=Repic Lampret |first3=Barbka |last4=Kovac |first4=Jernej |last5=Groselj |first5=Urh |last6=Tesovnik |first6=Tine |last7=Battelino |first7=Tadej |last8=Debeljak |first8=Marusa |date=2021-05-26 |title=Next-Generation Sequencing in Newborn Screening: A Review of Current State |journal=Frontiers in Genetics |volume=12 |doi=10.3389/fgene.2021.662254 |doi-access=free |issn=1664-8021 |pmc=8188483 |pmid=34122514}}</ref> For instance, targeted gene panels and [[whole-exome sequencing]] (WES) are used to identify disease causing missense mutations in genes associated with treatable conditions, such as [[severe combined immunodeficiency]] (SCID) and [[cystic fibrosis]]. Studies like the BabyDetect project have demonstrated the utility of genomic screening in identifying disorders missed by conventional methods, with actionable results for conditions affecting more than 400 genes.<ref name="Boemer_2025">{{cite journal | vauthors = Boemer F, Hovhannesyan K, Piazzon F, Minner F, Mni M, Jacquemin V, Mashhadizadeh D, Benmhammed N, Bours V, Jacquinet A, Harvengt J, Bulk S, Dideberg V, Helou L, Palmeira L, Dangouloff T, Servais L | title = Population-based, first-tier genomic newborn screening in the maternity ward | journal = Nature Medicine | volume = | issue = | pages = | date = January 2025 | pmid = 39875687 | doi = 10.1038/s41591-024-03465-x  | doi-access = free | pmc = 12003153 }}</ref><ref>{{cite book | vauthors = Rai P, Mamcarz EK, Hankins JS | chapter = Newborn Genetic Screening for Blood Disorders | veditors = de Alarcón PA, Werner EJ, Christensen RD | title = Neonatal Hematology: Pathogenesis, Diagnosis, and Management of Hematologic Problems | edition = 3rd | date = 2021 | publisher = Cambridge University Press | location = Cambridge |isbn=978-1-108-48898-3 }}</ref> In addition, genomic approaches allow for the detection of rare or recessive conditions that may not manifest biochemically at birth, significantly expanding the scope of diseases screened.<ref name="pmid37656463">{{cite journal | vauthors = Jiang S, Wang H, Gu Y | title = Genome Sequencing for Newborn Screening-An Effective Approach for Tackling Rare Diseases | journal = JAMA Network Open | volume = 6 | issue = 9 | pages = e2331141 | date = September 2023 | pmid = 37656463 | doi = 10.1001/jamanetworkopen.2023.31141 | url = | doi-access = free }}</ref> These advancements align with the established principles of NBS, which emphasize early detection and intervention to prevent morbidity and mortality.<ref>{{cite book | vauthors = Clarke JT | chapter = Newborn screening. | title = A Clinical Guide to Inherited Metabolic Diseases. | location = Cambridge | publisher = Cambridge University Press | date = 2005 | pages = 228–240 | isbn = 978-0-511-54468-2 | doi = 10.1017/CBO9780511544682.011 }}</ref>