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Of Mutations (of + mutation)

Distribution by Scientific Domains

Life Sciences	75%

Kinds of Of Mutations

variety of mutation

Selected Abstracts

One gene, two phenotypes: ROR2 mutations in autosomal recessive Robinow syndrome and autosomal dominant brachydactyly type B,

HUMAN MUTATION, Issue 1 2003
Ali R. Afzal
Abstract Autosomal recessive Robinow syndrome (RRS) is a severe skeletal dysplasia with short stature, generalized limb shortening, segmental defects of the spine, brachydactyly, and a dysmorphic facial appearance. The gene encoding receptor orphan receptor tyrosine kinase 2 (ROR2) is located on chromosome 9q22 and homozygous loss-of-function mutations in this gene are responsible for RRS. Moreover, knocking out the mouse Ror2 gene causes mesomelic dwarfism in the homozygous state, with almost identical features to recessive Robinow syndrome. The protein product of this gene is a cell membrane receptor, containing distinct motifs including an immunoglobulin-like (Ig) domain, a Frizzled-like cysteine-rich domain (FRZ or CRD), and a kringle domain (KD) in the extracellular region; and an intracellular region with tyrosine kinase (TK), serine/threonine-rich, and proline-rich structures. The extracellular motifs of the ROR2 protein are known to be involved in protein,protein interactions. The tyrosine kinase domain is involved in an as yet uncharacterized signaling pathway. Interestingly, heterozygous mutations in ROR2 have recently been shown to give rise to autosomal dominant brachydactyly type B1 (BDB1). This condition is characterized by terminal deficiency of fingers and toes. A variety of mutations have been reported in ROR2. Here, these genetic defects are compiled and possible genotype,phenotype correlations are discussed. Hum Mutat 22:1,11, 2003. © 2003 Wiley-Liss, Inc. [source]

Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiency

HUMAN MUTATION, Issue 4 2001
Luigi D. Notarangelo
Abstract During the last 10 years, an increasing number of genes have been identified whose abnormalities account for primary immunodeficiencies, with defects in development and/or function of the immune system. Among them is the JAK3 -gene, encoding for a tyrosine kinase that is functionally coupled to cytokine receptors which share the common gamma chain. Defects of this gene cause an autosomal recessive form of severe combined immunodeficiency with almost absent T-cells and functionally defective B-cells (T,B+ SCID). Herewith, we present molecular information on the first 27 unique mutations identified in the JAK3 gene, including clinical data on all of the 23 affected patients reported so far. A variety of mutations scattered throughout all seven functional domains of the protein, and with different functional effects, have been identified. Availability of a molecular screening test, based on amplification of genomic DNA, facilitates the diagnostic approach, and has permitted recognition that JAK3 deficiency may also be associated with atypical clinical and immunological features. Development of a structural model of the JAK3 kinase domain has allowed characterization of the functional effects of the various mutations. Most importantly, molecular analysis at the JAK3 locus results in improved genetic counseling, allows early prenatal diagnosis, and prompts appropriate treatment (currently based on hematopoietic stem cell transplantation) in affected families. Hum Mutat 18:255,263, 2001. © 2001 Wiley-Liss, Inc. [source]

Androgen insensitivity and male infertility,

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2003
O. Hiort
Summary Abnormal human spermatogenesis can be caused by defects in androgen action because of androgen insensitivity. A variety of mutations have been described in the human androgen receptor gene associated with male infertility. These can be attributed to two molecular mechanisms. First, point mutations in the androgen receptor gene cause alterations in the amino acid sequence and, hence, lead to apparently slight changes in the androgen receptor effector mechanisms and mild androgen insensitivity. Secondly, variations in the polymorphic poly glutamine segment within the N-terminal end of the androgen receptor have been ascribed to correlate with fertility aspects possibly because of modifications of transcriptional regulatory mechanisms. It has been postulated that longer poly glutamine segments are associated with decreased sperm counts. However, the molecular mechanisms that lead to inhibition of spermatogenesis because of a mutated androgen receptor are poorly understood and will need more focus in the future. [source]

Serotonin receptors antagonistically modulate Caenorhabditis elegans longevity

AGING CELL, Issue 4 2007
Hana Murakami
Summary The neurotransmitter serotonin has been implicated in affecting the variation of longevity in natural Drosophila populations and age-related diseases in mammals. Based on these observations, it has been predicted that serotonin signal, perhaps at levels of serotonin biosynthesis, may control lifespan. Here, we investigated a variety of mutations in serotonin-signal genes, including serotonin biosynthesis genes, a serotonin transporter gene, and serotonin receptor genes. Despite this prediction, mutations in the serotonin biosynthesis genes had little or modest effects on lifespan, while the mod-5 mutation with increased availability of serotonin caused a modest life-shortening effect. In contrast, a deletion mutation of the ser-1 serotonin receptor gene increased longevity by up to 46%, likely through the insulin/insulin-like growth factor 1 pathway. This result suggests an interaction between the serotonin pathway and the insulin/insulin-like growth factor 1 pathway. A deletion mutation of another serotonin receptor gene, ser-4, shortened early to mid lifespan. The results suggest that serotonin signal antagonistically modulates longevity through different serotonin receptors. This study may indicate serotonin receptors as a potential target for antigeric interventions. [source]