Editing Hemoglobinopathy (section)

==== Structural abnormalities ====
Hemoglobin structural variants manifest a change in the structure of the Hb molecule. The majority of hemoglobin variants do not cause disease and are most commonly discovered either incidentally or through newborn screening. Hb variants can usually be detected by protein-based [[assay]] methods such as [[Hemoglobin electrophoresis|electrophoresis]],<ref>{{Cite web |title=Hemoglobin Electrophoresis: MedlinePlus Medical Test |url=https://medlineplus.gov/lab-tests/hemoglobin-electrophoresis/ |access-date=2024-11-20 |website=medlineplus.gov |language=en}}</ref> [[isoelectric focusing]],<ref>{{Citation |last=Garfin |first=David E. |title=[35] Isoelectric focusing |date=1990 |journal=Methods in Enzymology |volume=182 |pages=459–477 |editor-last=Deutscher |editor-first=Murray P. |url=https://linkinghub.elsevier.com/retrieve/pii/0076687990820373 |access-date=2024-11-20 |series=Guide to Protein Purification |publisher=Academic Press |doi=10.1016/0076-6879(90)82037-3 |isbn=978-0-12-182083-1 |pmid=2314254}}</ref> or [[high-performance liquid chromatography]].<ref name="Arishi-2021">{{Cite journal |last1=Arishi |first1=Wjdan A. |last2=Alhadrami |first2=Hani A. |last3=Zourob |first3=Mohammed |date=2021-05-05 |title=Techniques for the Detection of Sickle Cell Disease: A Review |journal=Micromachines |language=en |volume=12 |issue=5 |pages=519 |doi=10.3390/mi12050519 |pmc=8148117 |pmid=34063111 |doi-access=free}}</ref> Diagnosis is commonly confirmed by [[DNA sequencing]].<ref name="Arishi-20212">{{Cite journal |last1=Arishi |first1=Wjdan A. |last2=Alhadrami |first2=Hani A. |last3=Zourob |first3=Mohammed |date=2021-05-05 |title=Techniques for the Detection of Sickle Cell Disease: A Review |journal=Micromachines |language=en |volume=12 |issue=5 |pages=519 |doi=10.3390/mi12050519 |pmc=8148117 |pmid=34063111 |doi-access=free}}</ref>

The hemoglobin structural variants can be broadly classified as follows:<ref>{{Cite journal |last=Forget |first=Bernard G. |last2=Bunn |first2=H. Franklin |date=2013-02-01 |title=Classification of the Disorders of Hemoglobin |url=https://perspectivesinmedicine.cshlp.org/content/3/2/a011684 |journal=Cold Spring Harbor Perspectives in Medicine |language=en |volume=3 |issue=2 |pages=a011684 |doi=10.1101/cshperspect.a011684 |issn=2157-1422 |pmc=3552344 |pmid=23378597}}</ref>
* '''[[Sickle cell disease|Sickle cell disorders]]''', which are the most prevalent form of hemoglobinopathy. Sickle hemoglobin (HbS) is prone to [[polymerizes|polymerize]] when deoxygenated, precipitating within the red blood cell. This damages the RBC membrane resulting in its premature destruction and consequent anemia.<ref>{{Cite journal | doi=10.1016/S0065-3233(08)60287-9| pmid=2195851| isbn=9780120342402| title=Sickle Cell Hemoglobin Polymerization | journal=Advances in Protein Chemistry| year=1990| last1=Eaton| first1=William A.| last2=Hofrichter| first2=James| volume=40| pages=63–279}}</ref>
* '''Unstable hemoglobin variants''' are mutations that cause the hemoglobin molecule to [[precipitate]], spontaneously or upon [[oxidative stress]], resulting in [[hemolytic anemia]]. Precipitated, [[Denaturation (biochemistry)|denatured]] hemoglobin can attach to the inner layer of the [[plasma membrane]] of the red blood cell (RBC) forming [[Heinz bodies]], leading to premature destruction of the RBC and anemia.<ref>{{cite journal | pmid = 7655024 | year = 1995 | last1 = Srivastava | first1 = P. | last2 = Kaeda | first2 = J. S. | last3 = Roper | first3 = D. | last4 = Vulliamy | first4 = T. J. | last5 = Buckley | first5 = M. | last6 = Luzzatto | first6 = L. | title = Severe hemolytic anemia associated with the homozygous state for an unstable hemoglobin variant (Hb Bushwick) | journal = Blood | volume = 86 | issue = 5 | pages = 1977–1982 | doi = 10.1182/blood.V86.5.1977.bloodjournal8651977 | doi-access = free }}</ref>
* '''Change in oxygen affinity.''' High or low oxygen affinity hemoglobin molecules are more likely than normal to adopt the relaxed (R, oxy) state or the tense (T, deoxy) state, respectively. High oxygen affinity variants (R state) cause [[Polycythemia vera|polycythemia]] (e.g., Hb Chesapeake, Hb Montefiore). Low oxygen affinity variants can cause [[cyanosis]] (e.g., Hb Kansas, Hb Beth Israel).<ref name="auto">{{cite journal | pmid = 19734427 | year = 2009 | last1 = Percy | first1 = M. J. | last2 = Butt | first2 = N. N. | last3 = Crotty | first3 = G. M. | last4 = Drummond | first4 = M. W. | last5 = Harrison | first5 = C. | last6 = Jones | first6 = G. L. | last7 = Turner | first7 = M. | last8 = Wallis | first8 = J. | last9 = McMullin | first9 = M. F. | title = Identification of high oxygen affinity hemoglobin variants in the investigation of patients with erythrocytosis | journal = Haematologica | volume = 94 | issue = 9 | pages = 1321–1322 | doi = 10.3324/haematol.2009.008037 | pmc = 2738729 }}</ref>