Dissertation > Excellent graduate degree dissertation topics show

Two Novel Mutations of DSRAD Gene in Chinese Families with Dyschromatosis Symmetrica Hereditaria

Author: ZhangYaJun
Tutor: ZhengRui
School: Shanxi Medical
Course: Dermatology and Venereology
Keywords: The hereditary symmetry pigment abnormalities Gene Mutation
CLC: R758.5
Type: Master's thesis
Year: 2011
Downloads: 23
Quote: 0
Read: Download Dissertation

Abstract

Research Background: a hereditary symmetry Dyschromatosis (dyschromatosis symmetrica of hereditaria, DSH, OMIM27400), also known as symmetry acral pigmentary abnormalities the disease (Symmet ric dyschromatosis of the the ext remities) or of Dohi acral pigmentation, is a relatively rare autosomal dominant hereditary skin disease, common in Asia, to be seen in a lot of cases reported in China and Japan, also found in Europe, India. DSH generally onset in infancy or early childhood to adolescence significantly slow progress and continued lifelong. Damage symmetrically distributed in the extremities and hand, foot and back, severe cases can affect the body. Lesions as punctate to soy or greater tawny to brown spotted, not integration, similar to freckles, intermingled hypopigmented spots, interwoven into a network. Summer can aggravate patients are usually no symptoms, but the disease seriously affects the appearance, patients might cause a heavy burden of thinking. Most of the patients in addition to the typical skin manifestations, no other system abnormalities. Occasionally the disease with ichthyosis vulgaris idiopathic allergic dystonia, idiopathic brain calcification, neurofibroma, neuropsychiatric system abnormalities reported. Clinically the disease xeroderma pigmentosum disease, mesh extremities pigment calm, the generalized Dyschromatosis differentiated. Miyamura in 2003 the pathogenic genes positioned as a double-stranded RNA-specific adenosine deaminase gene (double-stranded RNA-specific adenosine deaminase DSRAD). Widely expressed DSRAD addition to the skeletal muscle tissue in a mammal that can selectively edit the glutamate-gated receptor channel (GluR) the adenine nucleoside on the pre-mRNA deaminated transition into inosine, this process can resulting in the diversity of the protein, it can be changed by changing the amino acid sequence of the protein's function; miRNA target recognition can also influence by changing the cleavage site. Objective: To detect the three DSH pedigree DSRAD gene mutations. Explore the hereditary symmetry Dyschromatosis pedigree pathogenic mechanisms. The Research DSRAD gene mutation sites may play a role in the metabolism of skin pigmentation: Get the informed consent of patients, extracted three the DSH family members a total of 16 peripheral blood 3-5ml, while selecting the three families had no blood 100 normal adult relationship and no pigment diseases served as controls. With 2? TA anticoagulant removed erythrocytes, extraction of genomic DNA. Under DSRAD gene sequence to design 16 of the PCR primers used to amplify all the exons of the DSRAD gene coding region, and both ends of at least 40bp of intron sequence. DNA polymerase chain reaction amplification (Eppendorf, Germany), the PCR reaction, the reaction conditions were 94 ℃ for 56 ° C renaturation, 72 ° C extends 1min, 35 cycles. After the end of the thermal cycling, the PCR product with 1.5% agarose electrophoresis. With the direct sequencing DSRAD gene for detection. If the product of the correct size, no nonspecific products, used column purified PCR product was then sequenced. Re for bit mutations identified in order to ensure the accuracy of the results, the proband PCR, confirmed by repeated sequencing from another direction and then the opposite side of the primer. Proband in family B detect loss of heterozygosity mutations, the PCR product was cloned into the T vector, and then pick the selection of a number of clones sequenced to confirm. Results: after sequencing found that there are three families DSRAD abnormal gene. A No. 3 of the pedigree exon nucleotide 1760 A → G heterozygous mutation in the corresponding 587 tyrosine is cystine alternative to; pedigree C No. 15 exon of 3260 base G → T heterozygous mutation, corresponding to 1207 of glycine by valine substitution. This is the two newly discovered mutations. Pedigree C proband parents and other family members did not find the corresponding mutation analysis from the paternity test results, this mutation as a de novo mutation. The pedigree B the exon c.2433-2434 delAG mutation. The home is not sick and healthy subjects found no corresponding mutation. 3 conclusions: (1) genetic symmetry pigmentation disorder pedigrees the existence DSRAD gene-specific mutations, the study found two new mutations and a reported mutation. (2) or more mutations may make the protein functional defects, leading to clinically abnormal skin pigmentation. 90 Summary DSRAD gene mutation, found no clear correlation between genotype and phenotype of DHS.

Related Dissertations

CLC: > Medicine, health > Dermatology and Venereology > Dermatology > Congenital skin disease
© 2012 www.DissertationTopic.Net Mobile