Description of the disease and its clinical features.
Sickle cell disorder is a single genetic condition linked with progressive organ damage and acute illness episodes. The disease results from haemoglobin polymerization thus leading to vasoocclusion and erythrocyte rigidity. According to Bethesda (2008), the most common known cause of the disorder is the Hbs variant. The disorder is an autosomal recessive condition resulting from a point mutation that affects the Haemoglobin beta gene whose location is on chromosome 11. The disease clinical features include frequent cough, leg and joint aches, increasing fatigue, abdominal pains, night sweats and poor appetite. A person with sickle cells also manifests a correlation between oxygen tensions and red blood cells sickling in vivo (Bethesda, 2008). Positive clinical examination on a patient who has contracted the disease indicates aggregation of the disorder cells in sinuses with a patient blood vessels depicting lowered oxygen tension. Patients also experience priapism. Sickle cell disease in children manifests itself through slowed growth and development.
Additional features include aplastic, haemolytic and vaso-occlusive as well as sequestration crisis. The most common experience among patients with sickle cell diseases in pain (Piel, Steinberg & Rees, 2017). The pain manifestation is an early warning sign connected to vaso-occlusion and other complications that could be life threatening. The vaso-occlusive state results into a myriad of diagnostic considerations. The condition can also manifest itself through leg ulceration as well as osteomyelitis. Incidences of proliferative retinopathy can also result in a patient’s eyes. Dehydration in the urinary tract is a common clinical feature which can lead to renal failure. Pneumonia can occur in a patient’s pulmonary system as well as sickle cell chest condition. Cholelithiasis in young adult sickle cell patients can manifest too. Patients with sickle cell disorder are prone to stroke and other accompanying diseases such as streptococcus pneumoniae. According to Rees and Gibson (2012), the disorder is most prevalent in populations having an African descent.
Delegate your assignment to our experts and they will do the rest.
Inheritance of the disease
Regarding inheritance, sickle cell diseases has an autosomal recessive pattern implying that the gene copies have cell mutations in each. For the diseases to develop, both copies of its abnormal genes have to be present. Each of the parent of a person who has contracted an autosomal recessive disorder carries a copy of the disorder’s mutated gene. An individual carrying the copy of the sickle cell mutated gene is termed as a carrier. The probability of giving birth to a child with the condition from two people who are carriers of an autosomal recessive condition stands at 25% (Omim.org, n.d). There is also a 50% likelihood that a child born will be a carrier and a 25% (1 in 4) possibility that the condition will not be passed to the child thus implying that the child will not be a carrier (Rees & Gibson, 2012). If one’s partner has contracted the condition, there is a possibility that the disorder can be inherited by children. In the event the two parents are HbAA and/or HbSs carriers. Thus, infants born would acquire the same combination of the gene.
Gene Locus
Gene locus or loci describes the specific location on a chromosome where a particular gene has its position. The sickle cell disorder results from alteration in haemoglobin beta gene located on chromosome 11 at its tip. The sickle cell trait is located on recessive haemoglobin gene allele (Piel et al., 2017). The sickle cell anaemia has HBB gene locus. The chromosome 11 which is where the gene is on is a representation of 4 and 4.5 percent of the aggregate cell’s DNA (Omim.org, n.d). The shorter arm of the chromosome is referred to as 11p whereas the chromosomal longer arm is termed to as 11q. The chromosome 11 provides instructions in performance of variety of roles in a human body.
The sickle cell disorder phenotype MIM number is 603903 with its phenotype mapping key being 3 and 11p15.4 indicating its location.
Known Mutations
Single cell disorder has a single point mutation which is termed to as missense mutation. The point mutation has three known mutations namely, substitution, deletion and insertion mutations. As Piel et al., (2017) explains, the mutation occurs in the beta-hemoglobin gene that is responsible of converting GAG codon into GUG. The point mutation results to one nucleotide hemoglobin gene alteration. The mutation leads to distortion of the red blood cells hence assuming the shape of a sickle cell. The sickle cell cuts off circulation owing to clogging in the capillaries. The beta globin gene mutation alters amino acid thus leading to devastating outcomes (Pauling, Itano, Singer & Wells, 2009). The result of the gene mutation is misshapened blood cells that clog capillaries leading to a cut off blood supply to body tissues due to a single nucleotide mutation (Omim.org, n.d). The protein loses its function when elongated cells get stuck thus curtailing supply of blood to other parts of the body. The mutation leads to alteration of one of the hemoglobin protein’s amino-acids. The normal function of red blood cells is thus affected
References
Bethesda MD: (1998). Genes and Disease , National Center for Biotechnology Information (US) .
Omim.org(n.d). Sickle cell anemia, https://omim.org/entry/603903?search=sickle%20cell%20disease&highlight=cell%20disease%20sickle .
Piel, F. B., Steinberg, M. H., & Rees, D. C. (2017). Sickle cell disease. New England Journal of Medicine , 376 (16), 1561-1573.
Pauling, L., Itano, H. A., Singer, S. J., & Wells, I. C. (2009). Sickle cell anemia, a molecular disease. Science , 110 (2865), 543-548.
Rees, D. C., & Gibson, J. S. (2012). Biomarkers in sickle cell disease. British journal of haematology , 156 (4), 433-445.
