Lysosomal Porage Diseases Case Study

their normal shape to an abnormal shape, however, the chemical composition of the protein remains

Clinical examination and urine test (excess muccopolysaccharides are excreted in the urine) are the first steps in the diagnosis of an MPS disease. Enzymes assays ( testing a variety of cells or blood in culture for enzymes deficiency ) are also used to provide definitive diagnosis of one of the MPS. Prenatal diagnosis using amniocentesis and choroionic villus sampling can verify if the fetus is affected with the disorder. Genetic counseling can help parents who have a family history of the MPS to determined if they are carrying the mutated gene that causes the disorder.

mutation is phenylalanine 508 known as delta F508. Delta F508 is a deletion of 3 nucleotides

Classical, Hypermobility, Vascular and Arthrochalasia forms of EDS are transmitted as an autosomal dominant trait. Kyphoscoliosis and Dermatosparaxis type of EDS are transmitted as an autosomal recessive trait. Classical EDS results from a faulty collagen V genes. A decrease in collagen synthesis generally results in defective tissue mechanical properties and is mainly characterized by skin hyper extensibility (Bancelin, 2015). The Vascular Type of EDS is caused by structural defects in the proa1 (III) chain of collagen type III. Kyphoscoliosis Type EDS is the result of a deficiency of a collagen-modifying enzyme (lysylhydroxylase). The Arthrochalasia Type of EDS results from a mutation which leads to the deficient processing of the amino-terminal end of proa1(I) [type A] or proa2(I)[type B] chains of collagen type I. Dermatosparaxis Type EDS is caused by a deficiency of procollagen I N-terminal peptidase (ENDF,

Lysosomal storage diseases form due to the modification of lysosomal enzymes. The diseases can be metabolically inherited through gene mutation. In “Lysosomal Storage Disease”, Michael Kruer (2) claims that,

Describe the molecular nature and the inheritance pattern of the disease/disorder, ensuring to cite the original research paper that first identified specific genetic & molecular nature of the disease.

Although, chromosome 17 contains multiple genes and each cell contributes to the condition. The loss of the RAI1 gene is considered to be the main source of the syndrome. It has also been seen in a small percentage of the affected that rather than a full deletion of the RAI1 gene, they have minor mutations within the gene that cause variations of the disease. Provided that many individuals with just minor mutations may experience some of these symptoms; they are less likely to show some of the physical attributes that come alongside the full deletion of the RAI1

What is the disease? What is the mutation that is associated with the disease? What is known about how the mutation reported in the Journal article results in the disease

Multiple types of mutations can occur within the IL2RG gene. These include point mutations, deletions and insertions, and splice mutations. The deletions and insertions are seen on both a microscopic scale (one exon) or a macroscopic scale (four or more exons.) Five major locations for point mutations include cDNA 684T, cDNA 690T, cDNA 691T, cDNA 868A, and cDNA 879T, all of which are CG dinucleotides. Mutations of exon3(-15)g, the branch point adenosine, is also a common mutation. 26% of all cases of X-linked SCID are

A lot has to be learned about SMS, however, molecular analysis of the RAI1 gene, could be promising in the development of SMS Clinical Prediction Rules by using mutation prediction programs such as POLYPHEN, PANTHER, and PMUT. In a research conducted by Vilboux et al. (2011) two SMS clinical features demonstrated noticeable relationship to the RAI1 mRNA levels: ocular anomalies (Mann -Whitney Z= - 2.35; p=0.0188 and object insertion (Mann -Whitney Z = - 2.21; p=0.03.)

Clinically nine genes found which can cause PHHI(ABCC8, KCNJ11, GLUD1, GCK, HNF4A, HNF1A, SLC16A1,UCP2 and HADH)but most common are characterized by KCNJ11 and ABCC8 which is connected with ATP sensitive KATP channel of KIR6.2 and SUR1. It is assume that mutation

Once the MEPC2 gene was implicated in RTT there was an intense period of cohort screening in an attempt to elucidate genotypic-phenotypic associations (Weaving, 2005). As it stands there are an approximate 800 pathogenetic mutations that are currently found within the MEPC2 (Cheadle, 2000). These include missense, nonsense, frame shifts and inversions as well as large deletions which have now been identified as being present in 15% of apparently MECP2 mutation negative individuals. These large deletions would have gone undetected without the application of NGS techniques (Weaving, 2005). Work by Wolffe aimed to explore the associations between the type of MECP2 mutation and the degree of phenotypic severity. While work in this area is largely conflicted his study was concurrent with previous work concerning the view that particular mutations that were either point mutations, such as p.Arg133Cys, p.Arg294X, p.Arg306Cys and 3’ truncations resulted in a reduction in the severity of symptoms. There is also a wide consensus that missense mutations produce a less acute phenotype than nonsense mutations and that the most severe clinical features were the consequence of splice sites or large insertions or deletions (Weaving, 2005). The MEPC2 gene codes a protein, which is apart of the methyl-CpG-binding family. It contains three conserved functional domains. Work by Wolffe also examined which aspects of the protein were affected by each type of mutation. He found that Nonsense

genetics, a causative mutation could be mapped to a chromosomal region using linkage analysis of

3.2 IDUA enzyme activity increase in tissues of treated MPS I mice after 8 weekly infusions of IDUAL

which the enzyme denatures, will also vary. An enzyme is a protein and will denature like other