Degré Bloom, une mesure de la force en gelée d'une solution de gélatine; Bloom Energy, une entreprise américaine, fabricant de piles à combustible à oxydes solides; Effet bloom, le flou lumineux, un effet graphique utilisé en infographie; Filtre de Bloom, en informatique, une structure de données probabiliste; Syndrome de Bloom, une maladie génétique They also have extreme cutaneous photosensitivity (sensitivity to sunlight), neurodevelopmental abnormalities, and deafness, and often exhibit lipoatrophy, atrophic skin, severe tooth decay, sparse hair, calcium deposits in neurons, cataracts, sensorineural hearing loss, pigmentary retinopathy, and bone abnormalities. [20] These DNA damages, chromosome aberrations and mutations may in turn cause more RecQ-independent aging phenotypes. This explains why the populace sides of the Jews are more knowledgeable and familiar with this condition compared to the others. [citation needed], Trichothiodystrophy (TTD) is a rare autosomal recessive disease whose symptoms span across multiple systems[56] and can vary greatly in severity. Genetics. The mean age of diagnosis is twenty-four. [56], TTD is caused by mutations in one of three genes, ERCC2, ERCC3, or GTF2H5, the first two of which are also linked to xeroderma pigmentosum. Repair of DNA double-strand breaks can occur by one of two processes, non-homologous end joining (NHEJ) or homologous recombination (HR). Humans have a total of 46 chromosomes. Damage to the DNA maximizes the risk of multiple cancers in the initial years o… First described by New York dermatologist Dr. David Bloom in 1954. Zespół Blooma (ang. Approximately one-third of individuals who have BS are of Ashkenazi Jewish descent. Upload media Wikipedia Instance of: disease, developmental defect during embryogenesis, rare disease: Subclass of: autosomal recessive disease, genetic photodermatosis, polymalformative genetic syndrome with increased risk of developing cancer, inherited skin tumor, Restrictive dermopathy (RD), also called tight skin contracture syndrome, is a rare, lethal autosomal recessive perinatal genodermatosis. Wiedemann–Rautenstrauch (WR) syndrome, also known as neonatal progeroid syndrome,[91] is an autosomal recessive progeroid syndrome. 예. Mutations may also lead to the truncation (shortening) of the WRNp protein, leading to the loss of its nuclear localization signal sequence, which would normally transport it to the nucleus where it can interact with the DNA. Individuals with XP have extreme sensitivity to light in the ultraviolet range starting from one to two years of age,[51] and causes sunburn, freckling of skin, dry skin and pigmentation after exposure. GeneRIFs: Gene References Into Functions. This term means that the chromosomes of affected people are unstable and can break easily. progerin or LaminAΔ50).[70]. People with BS start their life with a low weight and length when they are born. Bloom syndrome protein homolog, Bloom syndrome homolog, Bloom syndrome, RecQ helicase-like, mBLM, recQ helicase homolog. un retard de croissance pré et post-natal avec un poids de naissance moyen de 1,760 kg, certains sont eutrophes ;; un crâne plutôt étroit avec une impression que le maxillaire et la mandibulaire sont sous développés à l'inverse du nez et des oreilles ; Bloom syndrome (congenital telangiectatic erythema) is a rare autosomal recessive disease caused by a mutation on 15q26.1 leading to errors in DNA replication.. La malattia è stata descritta per la prima volta dal dermatologo David Bloom nel 1954 Quadro clinico. Most also develop photosensitivity, which causes the blood vessels to be dilated and leads to reddening of the skin, usually presented as a "butterfly-shaped patch of reddened skin across the nose and cheeks". Bloom syndrome is an incredibly rare disorder, with approximately 140 cases having been reported. Bloom syndrome strikes repeatedly before stealing the victim's shortened lives.. The variant form, XP-V, is caused by mutations in the POLH gene, which unlike the rest does not code for components of the NER pathway but produces a DNA polymerase that allows accurate translesion synthesis of DNA damage resulting from UV radiation; its mutation leads to an overall increase in UV-dependent mutation, which ultimately causes the symptoms of XP. Homologous recombination-Wikipedia Xeroderma pigmentosum mostly affects the eye and skin. Examples of PS include Werner syndrome (WS), Bloom syndrome (BS), Rothmund-Thomson syndrome (RTS), Cockayne syndrome … [5], The Bloom syndrome gene product is related to the RecQ subset of DExH box-containing DNA helicases and has both DNA-stimulated ATPase and ATP-dependent DNA helicase activities. Chromosomes, which are found in the nuclei of cells, carry genetic information. Das Bloom-Syndrom-Protein (RecQ2) ist ein Enzym, das in vielen Lebewesen im Zellkern vorkommt. Taiyou no Uta, a 2006 Japanese film, features Kaoru Amane (portrayed by Yui), a 16-year-old girl suffers from xeroderma pigmentosum. They tend to develop pigmentation changes and dilated blood vessels in the skin, particularly in response to sun exposure. Examples of PS include Werner syndrome (WS), Bloom syndrome (BS), Rothmund–Thomson syndrome (RTS), Cockayne syndrome (CS), xeroderma pigmentosum (XP), trichothiodystrophy (TTD), combined xeroderma pigmentosum-Cockayne syndrome (XP-CS), restrictive dermopathy (RD), and Hutchinson–Gilford progeria syndrome (HGPS). [citation needed], There is no evidence from the Bloom's Syndrome Registry or from the peer-reviewed medical literature that BS is a progeroid condition associated with advanced aging. Premature aging is a result of Mis-construction during development as a consequence of gene mutations, whereas normal aging is a result of accumulation of Misrepairs for the survival of an organism. More than 30 cases have been reported. Segmental progeria, which is more frequently associated with the term progeroid syndrome, tends to affect multiple or all tissues while causing affected individuals to exhibit only some of the features associated with aging. They affect only one tissue and can be classified as unimodal progeroid syndromes. Premature aging also develops on some animal models which have genetic alterations. The incidence rate of TTD is estimated to be 1.2 per million in Western Europe. Other characteristics of BS include learning disabilities, an increased risk of diabetes, gastroesophageal reflux (GER), and chronic obstructive pulmonary disease (COPD). The types of cancer and the anatomic sites at which they develop resemble the cancers that affect persons in the general population. Blooms syndrome is a very rare inherited genetic disorder. However, patients with TTD do not show a higher risk of developing skin cancer, in contrast to patients with XP. [66] The mean age of diagnosis is ~3 years and the mean age of death is ~13 years. Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that is associated with a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. 증상으로는 구토, 성격 변화, 혼란, 발작, 의식 불명을 포함한다. BS is caused by mutations in the BLM gene, which encodes for the Bloom syndrome protein, a RecQ helicase. Wikipedia Causes of Bloom's syndrome . During replication of the genome, the two copies of DNA, called sister chromatids, are held together through a structure called the centromere. Alternative form of Bloom's syndrome Bloom syndrome (uncountable) . DNA ligase joins the strands together to form dsDNA. [101], F. Scott Fitzgerald's 1922 short story The Curious Case of Benjamin Button is about a boy who was born with the appearance of a 70-year-old and who ages backwards. The budding yeast Saccharomyces cerevisiae encodes an ortholog of the Bloom syndrome (BLM) protein that is designated Sgs1 (Small growth suppressor 1). [79], Individuals with RD exhibit growth retardation starting in the uterus, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, abnormal facial features (small mouth, small pinched nose and micrognathia), sparse or absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia and multiple joint contractures. You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA. Bloom syndrome is sometimes considered a disease of premature or accelerated aging. Seattle (WA): University of Washington, Seattle; 1993-. Presentation. [102] The description of the fictitious Smallweed family in the Charles Dickens' Bleak House suggests the characters suffered from progeria. Lizzie Velásquez is an American motivational speaker who has a syndrome that resembles progeria, although the exact nature is unclear; it is now thought to be a form of neonatal progeroid syndrome. Oshima J, Martin GM, Hisama FM. There is no treatment for the underlying cause of Bloom syndrome. It was first discovered by using the Giemsa staining method on one chromatid belonging to the sister … Bloom syndrome, also known as Bloom-Torre-Machacek syndrome or congenital telangiectatic erythema, is a rare genetic disease caused by a mutation in the BLM gene on chromosome 15q26.1, which encodes RECQL3 helicase. Parents do not necessarily have to present this disease; they may be carriers of … It is a rare form of inherited disorder that is also known as ‘ She was featured in the media.[96]. [58] More severe cases cause delayed development, significant intellectual disability, and recurrent infection; the most severe cases see death at infancy or early childhood. The most widely studied of the progeroid syndromes are Werner syndrome and Hutchinson–Gilford progeria, as they are seen to most resemble natural aging. [7], Werner syndrome (WS) is a rare autosomal recessive disorder. Mutationen im BLM-Gen sind Ursache für das Bloom-Syndrom, eine seltene Erbkrankheit.RecQ2 gehört zu den DEAD-Box-Helikasen und bindet an G-Quadruplexe. Bloom syndrome is characterized by genome instability.The most prominent features include short stature and a rash on the face that develops early in life when exposed to the sun. Mutations that cause Werner syndrome only occur at the regions of the gene that encode for protein and not at non-coding regions. Bloom syndrome From Wikipedia, the free encyclopedia Bloom syndrome (often ab­bre­vi­ated as BS in literature), also known as Bloom-Torre-Machacek syndrome, is a rare au­to­so­mal re­ces­sive dis­or­der char­ac­ter­ized by short stature, pre­dis­po­si­tion to the de­vel­op­ment of can­cer and ge­nomic instability. [1][2] The term progeroid syndrome does not necessarily imply progeria (Hutchinson–Gilford progeria syndrome), which is a specific type of progeroid syndrome. If a person has one affected gene, he or she is called a carrier of Bloom Syndrome and does not manifest symptoms of … After being translated, a farnesol is added to prelamin A using protein farnesyltransferase; this farnesylation is important in targeting lamin to the nuclear envelope, where it maintains its integrity. [64] This results in a truncated lamin A precursor (a.k.a. 라이 증후군(Reye syndrome)은 급속 진행성 뇌증이다. Paa, a 2009 Indian comedy-drama film, features a protagonist, Auro (Amitabh Bachchan), who has progeria. 조로증(早老症,Progeroid syndromes, Accelerated aging)은 빨리 늙는 병이다.조로증의 원인으로는 DNA 복구에 문제가 생긴 경우 등이 있다. Other names for Bloom Syndrome are Bloom-Torre Machacek Syndrome and Congenital Telangiectatic Erythema. DISCUSSION. However, unlike RecQ-associated PS, not all individuals affected by these diseases have increased risk of cancer. Further reading . In: Pagon RA, Bird TD, Dolan CR, et al., editors. 사망률은 라이 증후군 환자 중 20~40%에 달하며 생존자 중 약 3분의 1이 상당한 뇌손상을 겪는다. People with Bloom syndrome may be first diagnosed with cancer at about 25 years old. [41] The mean age of death is ~12 years,[42] although the different forms differ significantly. After birth, the child's normal growth is retarded, resulting in a short stature. La sindrome di Bloom (BSyn) è una rara malattia ereditaria caratterizzata da un'alta frequenza nella rottura e nel riarrangiamento dei cromosomi della persona affetta. This page is based on the copyrighted Wikipedia article "Bloom_syndrome" ; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License. Defective homologous recombination can cause mutation and genetic instability. After strand invasion, the further sequence of events may follow either of two main pathways leading to a crossover (CO) or a non-crossover (NCO) recombinant (see Genetic recombination and bottom of Figure in this section). [7], There are five genes encoding RecQ in humans (RECQ1-5), and defects in RECQL2/WRN, RECQL3/BLM and RECQL4 lead to Werner syndrome (WS), Bloom syndrome (BS), and Rothmund–Thomson syndrome (RTS), respectively. Bloom syndrome (BS) is a very rare autosomal recessive disorder. [97] Velásquez is an advocate of anti-bullying. All affected individuals have a 1000-fold higher risk of developing skin cancer:[53] half of the affected population develop skin cancer by age 10, usually at areas most exposed to sunlight (e.g. Thus the process of development and that of aging are coupled by Mis-construction and Mis-re-construction (Misrepair) of the structure of an organism. [50] There have been 830 published cases from 1874 to 1982. With fewer mRNA, fewer are available to be translated into the WRNp protein. It occurs at a rate of about 1 in 300,000-500,000 in the United States and Europe. Upload media Wikipedia: Instance of: disease, developmental defect during embryogenesis, rare disease: Subclass of: autosomal recessive disease, genetic photodermatosis, Mutations in the BLM gene (locus 15q26.1) cause Bloom syndrome. [34] Variants of these diseases, such as DeSanctis–Cacchione syndrome and Cerebro-oculo-facio-skeletal (COFS) syndrome, can also be caused by defects in the NER pathway. [3] Progeroid syndromes have been widely studied in the fields of aging, regeneration, stem cells, and cancer. If both parents are carriers, there is a one in four, or 25%, chance with each pregnancy for an affected child. Bloom syndrome protein has been shown to interact with: CS1 maint: DOI inactive as of November 2020 (, hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides, GO:1990163 four-way junction helicase activity, regulation of cyclin-dependent protein serine/threonine kinase activity, positive regulation of transcription, DNA-templated, double-strand break repair via homologous recombination, regulation of DNA-dependent DNA replication, resolution of meiotic recombination intermediates, double-strand break repair via nonhomologous end joining, meiotic DNA double-strand break processing involved in reciprocal meiotic recombination, double-strand break repair via synthesis-dependent strand annealing, negative regulation of mitotic recombination, positive regulation of alpha-beta T cell proliferation, negative regulation of thymocyte apoptotic process, resolution of recombination intermediates, negative regulation of double-strand break repair via single-strand annealing, positive regulation of double-strand break repair via homologous recombination, regulation of signal transduction by p53 class mediator, DNA unwinding involved in DNA replication, GRCh38: Ensembl release 89: ENSG00000197299, GRCm38: Ensembl release 89: ENSMUSG00000030528, "The Bloom's syndrome gene product is a 3'-5' DNA helicase", "BLM helicase ortholog Sgs1 is a central regulator of meiotic recombination intermediate metabolism", "Multiple mechanisms limit meiotic crossovers: TOP3α and two BLM homologs antagonize crossovers in parallel to FANCM", "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures", "Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM", "Physical and functional interaction between the Bloom's syndrome gene product and the largest subunit of chromatin assembly factor 1", "Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest", "Stimulation of flap endonuclease-1 by the Bloom's syndrome protein", "Cleavage of the Bloom's syndrome gene product during apoptosis by caspase-3 results in an impaired interaction with topoisomerase IIIalpha", "The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair", "Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1", "Functional interaction of p53 and BLM DNA helicase in apoptosis", "The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control", "The processing of Holliday junctions by BLM and WRN helicases is regulated by p53", "Functional interaction between the Bloom's syndrome helicase and the RAD51 paralog, RAD51L3 (RAD51D)", "Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51", "Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity", "Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases", "The Bloom's syndrome gene product interacts with topoisomerase III", "Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability", "Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins", "Elevated sister chromatid exchange phenotype of Bloom syndrome cells is complemented by human chromosome 15", "Bloom syndrome: an analysis of consanguineous families assigns the locus mutated to chromosome band 15q26.1", "Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom's syndrome", "Nuclear structure in normal and Bloom syndrome cells", "The Bloom's syndrome gene product promotes branch migration of Holliday junctions", "Cell cycle regulation of the endogenous wild type Bloom's syndrome DNA helicase", 10.1002/1098-1004(200006)15:6<584::AID-HUMU28>3.0.CO;2-I, "Potent inhibition of Werner and Bloom helicases by DNA minor groove binding drugs", "Cleavage of the Bloom's syndrome gene product during apoptosis by caspase-3 results in an impaired interaction with topoisomerase IIIα", GeneReviews/NCBI/NIH/UW entry on Bloom Syndrome, https://en.wikipedia.org/w/index.php?title=Bloom_syndrome_protein&oldid=994347210, DNA replication and repair-deficiency disorders, CS1 maint: DOI inactive as of November 2020, Short description is different from Wikidata, Creative Commons Attribution-ShareAlike License, Overview of all the structural information available in the, This page was last edited on 15 December 2020, at 06:45. BS causes infertility in males and reduced fertility and early-onset menopause in females. English [] Noun []. WR is associated with abnormalities in bone maturation, and lipids and hormone metabolism. 22 pairs of chromosomes plus a pair sex chromosome (X or Y) are inherited from each parent. Bloom 's syndrome (uncountable) A rare genetic disease characterized by stunted growth, predisposition to the development of cancer, and genomic instability. [17], Cells of affected individuals have reduced lifespan in culture,[18] more chromosome breaks and translocations[19] and extensive deletions. Bloom's Syndrome, or BSyn, is a rare genetic disorder that belongs to a group of conditions called chromosomal breakage syndromes. [47] The ubiquitinated RNAP II then dissociates and is degraded via the proteasome. A-type lamins promote genetic stability by maintaining levels of proteins which have key roles in NHEJ and HR. There are three excision repair pathways: nucleotide excision repair (NER), base excision repair (BER), and DNA mismatch repair (MMR). [66], HGPS is caused by sporadic mutations (not inherited from parent) in the LMNA gene, which encodes for lamin A. Of these, about one-third are from Central and Eastern European … [68], Individuals with HGPS typically appear normal at birth, but their growth is severely retarded, resulting in short stature, a very low body weight and delayed tooth eruption. [14] WRN encodes the WRNp protein, a 1432 amino acid protein with a central domain resembling members of the RecQ helicases. [82] The condition is caused by mutations near the 3'-terminus of the FBN1 gene. Misrepair-accumulation aging theory[88][89] suggests that the abnormality of tissue structure is the common point between premature aging and normal aging. Unfortunately, the average lifespan of persons with Bloom syndrome is 27 years; consequently, there is insufficient information to completely rule out the possibility that BS is associated with some features of aging. There are three types of CS, distinguished by severity and age of onset. El síndrome de Bloom (BLM), también conocido como síndrome de Bloom-Torre-Machacek, [1] es una enfermedad rara, genética con patrón hereditario autosómico recesivo [2] caracterizado por una alta frecuencia de rupturas y reordenamientos en los cromosomas de los afectados. Sister chromatid exchange (SCE) is the exchange of genetic material between two identical sister chromatids.. Thus, DNA helicases, such as RecQ, maintain the integrity of a cell, and defects in these helicases are linked to an increased predisposition to cancer and aging phenotypes. [39], Cockayne syndrome (CS) is a rare autosomal recessive PS. [3] All these disorders can be caused by mutations in a single gene, XPD,[35][36][37][38] or in other genes. Males with Bloom syndrome are often infertile and females may experience early menopause. Bloom's syndrome. The Sgs1(BLM) helicase appears to be a central regulator of most of the recombination events that occur during S. cerevisiae meiosis. Mutations causing Bloom syndrome delete or alter helicase motifs and may disable the 3' → 5' helicase activity. From as early as child hood, cancers of all kinds. Some segmental progeroid syndromes, such as Werner syndrome (WS), Bloom syndrome (BS), Rothmund-Thomson syndromes (RTS) and combined xeroderma pigmentosa-Cockayne syndrome (XP-CS), are associated with an increased risk of developing cancer in the affected individual; two exceptions are Hutchinson–Gilford progeria (HGPS) and Cockayne syndrome.[95]. Most affected individuals die in the uterus or are stillbirths, and liveborns usually die within a week. Here are links to possibly useful sources of information about Bloom syndrome. Bloom syndrome is a condition that causes varied health problems including diabetes, lung problems, skin that is sensitive to the sun, and increased risk of infections. Bloom syndrome (congenital telangiectatic erythema) is a rare autosomal recessive disorder. Medical Information Search. In the strand invasion step that follows, an overhanging 3' end of the broken DNA molecule then "invades" the DNA of an homologous chromosome that is not broken. There are two subpathways for NER, which differ only in their mechanism for recognition: global genomic NER (GG-NER) and transcription coupled NER (TC-NER). The baby has a high risk of being born prematurely and will have a low birth weight. I. Genetical and clinical observations in the first twenty-seven patients". These associations have led to the speculation that BS could be associated with aging. She has over thirteen million Facebook page views. Williams syndrome is caused by a genetic abnormality, specifically a deletion of about 27 genes from the long arm of one of the two chromosome 7s. The MPLKIP gene has been associated with this form of TTD, although it accounts for only 20% of all known cases of the non-photosensitive form of TTD, and the function of its gene product is also unclear. All disorders within this group are thought to be monogenic,[3] meaning they arise from mutations of a single gene. 여러 유형의 조로증이 있다. Bloom syndrome is caused by genetic variants in the BLM gene and is inherited in an autosomal recessive pattern. [citation needed]. HGPS is considered autosomal dominant, which means that only one of the two copies of the LMNA gene needs to be mutated to produce this phenotype. The normal protein may act to suppress inappropriate homologous recombination.[6]. [77] Mouse cells deficient for maturation of prelamin A show increased DNA damage and chromosome aberrations and have increased sensitivity to DNA damaging agents. When the truncated prelamin A is localized to the nuclear envelope, it will not be processed and accumulates,[71] leading to "lobulation of the nuclear envelope, thickening of the nuclear lamina, loss of peripheral heterochromatin, and clustering of nuclear pores", causing the nucleus to lose its shape and integrity. Approximately one-third of individuals who have BS are of Ashkenazi Jewish descent. [100] His fame came about after a documentary in 2008 on TV 2 about Sørensen. In the plant Arabidopsis thaliana, homologs of the Sgs1(BLM) helicase act as major barriers to meiotic CO formation. Bloom syndrome is an autosomal recessive inherited disorder, which means that two abnormal Bloom syndrome genes are needed for the disease to be apparent (one from each parent). They may decrease the stability of the transcribed messenger RNA (mRNA), which increases the rate at which they are degraded. They have physical abnormalities including a large head (macrocephaly), sparse hair, prominent scalp veins, inward-folded eyelids, widened anterior fontanelles, hollow cheeks (malar hypoplasia), general loss of fat tissues under the skin, delayed tooth eruption, abnormal hair pattern, beaked noses, mild to severe mental retardation and dysmorphism. Even as adults, they typically remain under 5 feet tall. GeneReviews™ [Internet]. While mild to moderate intellectual disability with particular problems with visual spatial tasks such as drawing is typical, verbal skills are generally relatively unaffected. Individuals with defects in these genes often have developmental defects and exhibit neurodegeneration. Blooms Connect — a forum by and for people with Bloom’s Syndrome and their loved ones Bloom’s Syndrome Registry — research and information about Bloom’s Syndrome Bloom’s Syndrome Foundation — devoted to medical & scientific research to discover a treatment or cure for Bloom’s Syndrome In NER, the damaged DNA strand is removed and the undamaged strand is kept as a template for the formation of a complementary sequence with DNA polymerase. People with Bloom syndrome are usually smaller than 97 percent of the population in both height and weight from birth, and they rarely exceed 5 feet tall in adulthood. Typically this occurs as a random event during the formation of the egg or sperm from which a person develops. Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is not expressed in Bloom syndrome. [13] The median and mean age of death are 47-48 and 54 years, respectively;[14] the main cause of death is cardiovascular disease or cancer. [24] These mutations may be frameshift, missense, non-sense, or mutations of other kinds and are likely to cause deletions in the gene product. Permission is granted to copy, distribute and/or modify this document under the terms of the GNU Free Documentation License, Version 1.2 or any later version published by the Free Software Foundation; with no Invariant Sections, no Front-Cover Texts, and no Back-Cover Texts.A copy of the license is included in the section entitled "GNU Free Documentation License."