Genetic Basis of Distal Arthrogryposes

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Publication Type dissertation
School or College School of Medicine
Department Human Genetics
Author Toydemir, Reha
Title Genetic Basis of Distal Arthrogryposes
Date 2006-12
Description Every year millions of children are born with a birth defect. Birth defects, which can be described as abnormalities of structure or function that is present from birth, are the leading cause of infant death in developed countries and a significant cause of morbidity and economic burden in low- or middle-income countries. This dissertation addresses the genetic basis of distal arthrogryposes (DAs), a subgroup of birth defects that are characterized by contractures of the distal joints of a limb. Based on previous research of our laboratory, we hypothesized that DAs are defects of contractile apparatus in fast twitch skeletal myofibers and tested this hypothesis in four DA syndromes. We found that mutations of the embryonic myosin heavy chain gene cause DA2A and DA2B, whereas a missense mutation of the perinatal myosin heavy chain gene is responsible for DA7. Furthermore, we found mutations in the adult and extraocular myosin heavy chain genes in some DA5 patients. Furthermore, we noticed some patients with similar findings who do not meet the diagnostic criteria of the known DA syndromes. We proposed one of these conditions to be named as DA10, and mapped this condition to the long arm of chromosome 2. We named the other condition as the CATSHL syndrome, which we showed to be caused by a loss-of-function mutation in the fibroblast growth factor receptor 3 gene. The main contribution of this research is to benefit affected individuals and their families, since molecular testing can now be offered to them. In addition, through further studies leading to a better understanding of normal and abnormal development, effective strategies for prevention and treatment of congenital limb malformations can be developed.
Type Text
Publisher University of Utah
Subject MESH Pedigree; Syndrome; Phenotype; Congenital Abnormalities; Abnormalities, Multiple; Arthrogryposis; Limb Deformities, Congenital; Myosin Heavy Chains; Mutation; Mutation, Missense; Sequence Homology, Amino Acid
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital reproduction of Genetic Basis of Distal Arthrogryposes
Rights Management Copyright Reha Toydemir © 2006
Format Medium application/pdf
Format Extent 3,586,893 bytes
Identifier undthes,3945
Source Original in Marriott Library Special Collections
ARK ark:/87278/s6jq12wk
Setname ir_etd
Date Created 2012-04-24
Date Modified 2021-05-06
ID 191663
Reference URL https://collections.lib.utah.edu/ark:/87278/s6jq12wk
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