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Partial adenosine deaminase deficienciency without immunodeficiency: biochemical and genetic studiesHart, Stephen Lewis 29 April 2015 (has links)
A Thesis submitted to the Faculty of
Medicine, University of the Witwatersrand,
Johannesburg, for the Degree of
Master of Science
JOHANNESBURG 1986 / The adenosine deaminase enzyme from a Xhosa tribesman
has been characterized. Red blood cell activity levels
were 6-9% of normal whereas his white cell ADA levels
were about 30% of normal. The enzyme's stability at 57°C
was shown to be greatly reduced suggesting a mutation
resulting in an enzyme with reduced stability in vivo.
It was concluded that the discrepancy in ADA activity
levels between red and white blood cells was due to the
red cells being anucleate.
The proband's residual ADA was found to have a
Michaelis Constant (K ) for adenosine m of 47.9 ♦ IS.BuM,
a value which is not significantly different from that
of normal ADA (51.7 ± 11.4ufl).
Red cell deoxy-ATP levels were measured and found
to be elevated two-to-three times over normal levels.
Red cells from ADA-deficient patients with severe
combined immunodeficiency (SCID) have been reported
with deoxy-ATP levels elevated about 1 000 times. It
was concluded that the slight elevation of deoxy-ATP
levels in the proband were too low to have any noticeable
effect on functions of his immune system.
Starch gel electrophoresis of red cell ADA from
members of the proband's family in conjunction with red
cell ADA activity levels suggested that both parents
carried a gei e for 'partial' ADA deficiency, both of
which had been inherited by the proband as well as one
of his sibs. Isoelectric focusing studies suggested
that the two, parental AUA partial deficiency genes
were different from one another.
It was also found that another rare allele of ADA,
possibly ADA ',was segregating within the same family
although this event appaars to be unconnected with the
ADA partial deficiency.
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Genetic disorders on the island of MauritiusWallis, Colin E January 1988 (has links)
Inherited disorders are an important cause of physical handicap, deafness, mental retardation and blindness. There is considerable variation in the geographic and ethnic distribution of genetic disease due to biological pressures and historical accidents. In this context the relative prevalence of common inherited disorders and the recognition of rare conditions in isolated communities is of great academic importance. Oceanic islands are of special significance in the study of inherited disease. Virtually nothing has been documented concerning genetic disorders on the Island of Mauritius with a population of one million people. This study was undertaken to document the impact of inherited disorders on handicapping conditions in this community. As genetic disease concentrates in institutions, formal screening of all the schools for the deaf and blind, and the associations for the physically and mentally handicapped on Mauritius was undertaken. This involved a careful history, clinical examination and genealogical study, with radiographic, biochemical and ancillary testing performed where appropriate. Referral clinics were also established for the assessment of individuals and families known, or thought to be afflicted with abnormalities or handicap of a genetic origin. To ensure completeness, a similar survey was performed on Rodrigues, a neighbouring island, as this community is included under the responsibilities of the Mauritian Ministry of Health. Accumulated data concerning 681 patients were analysed. Genetic disorders accounted for disability in 265 individuals representing 38,6% of the causes of handicap. Of these persons 54 were deaf, 30 were blind, 99 were mentally retarded and 80 were physically handicapped. Several new entities, considered unique to the area and a consequence of either consanguinity or the founder effect, were documented. Karyotyping on selected individuals was undertaken in the laboratories of the Department of Human Genetics, University of Cape Town. A molecular genetic study of a large family with X-linked deafness of Nance, conducted by the same laboratory, revealed tight linkage with the probe pDP34; linkage analysis was performed on patients with Duchenne muscular dystrophy. The collation of these original data, the delineation of the new genetic conditions and an analysis of the results form the subject of this thesis and provide a basis for the future development of genetic services on Mauritius.
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Transmission genetics of pancreatic acinar atrophy in the German Shepherd Dog and development of microsatellite DNA-based tools for canine forensics and linkage analysisClark, Leigh Anne 30 September 2004 (has links)
The domestic dog, Canis lupus familiaris, has emerged as a model system for the study of human hereditary diseases. Of the approximately 450 hereditary diseases described in the dog, half have clinical presentations that are quite similar to specific human diseases. Understanding the genetic bases of canine hereditary diseases will not only complement comparative genetics studies but also facilitate selective breeding practices to reduce incidences in the dog. Whole genome screens have great potential to identify the marker(s) that segregate with canine hereditary diseases for which no reasonable candidate genes exist. The Minimal Screening Set-1 (MSS-1) was the first set of microsatellite markers described for linkage analysis in the dog and was, until recently, the best tool for genome screens. The MSS-2 is the most recently described screening set and offers increased density and more polymorphic markers. The first objective of this work was to develop tools to streamline genomic analyses in the study of canine hereditary diseases. This was achieved through the development of 1) multiplexing strategies for the MSS-1, 2) a multiplex of microsatellite markers for use in canine forensics and parentage assays and 3) chromosome-specific multiplex panels for the MSS-2. Multiplexing is the simultaneous amplification and analysis of markers and significantly reduces the expense and time required to collect genotype information. Pancreatic acinar atrophy (PAA) is a disease characterized by the degeneration of acinar cells of the exocrine pancreas and is the most important cause of exocrine pancreatic insufficiency (EPI) in the German Shepherd Dog (GSD). Although the prognosis for dogs having EPI is typically good with treatment, many dogs are euthanized because the owners are unable to afford the expensive enzyme supplements. The second objective of this work was to determine the mode of transmission of EPI in the GSD and conduct a whole genome screen for linkage. Two extended families of GSDs having PAA were assembled and used to determine the pattern of transmission. The results of this indicate that PAA is an autosomal recessive disease. The multiplexed MSS-1 was used to conduct an initial whole genome screen, although no markers were suggestive of linkage.
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Transmission genetics of pancreatic acinar atrophy in the German Shepherd Dog and development of microsatellite DNA-based tools for canine forensics and linkage analysisClark, Leigh Anne 30 September 2004 (has links)
The domestic dog, Canis lupus familiaris, has emerged as a model system for the study of human hereditary diseases. Of the approximately 450 hereditary diseases described in the dog, half have clinical presentations that are quite similar to specific human diseases. Understanding the genetic bases of canine hereditary diseases will not only complement comparative genetics studies but also facilitate selective breeding practices to reduce incidences in the dog. Whole genome screens have great potential to identify the marker(s) that segregate with canine hereditary diseases for which no reasonable candidate genes exist. The Minimal Screening Set-1 (MSS-1) was the first set of microsatellite markers described for linkage analysis in the dog and was, until recently, the best tool for genome screens. The MSS-2 is the most recently described screening set and offers increased density and more polymorphic markers. The first objective of this work was to develop tools to streamline genomic analyses in the study of canine hereditary diseases. This was achieved through the development of 1) multiplexing strategies for the MSS-1, 2) a multiplex of microsatellite markers for use in canine forensics and parentage assays and 3) chromosome-specific multiplex panels for the MSS-2. Multiplexing is the simultaneous amplification and analysis of markers and significantly reduces the expense and time required to collect genotype information. Pancreatic acinar atrophy (PAA) is a disease characterized by the degeneration of acinar cells of the exocrine pancreas and is the most important cause of exocrine pancreatic insufficiency (EPI) in the German Shepherd Dog (GSD). Although the prognosis for dogs having EPI is typically good with treatment, many dogs are euthanized because the owners are unable to afford the expensive enzyme supplements. The second objective of this work was to determine the mode of transmission of EPI in the GSD and conduct a whole genome screen for linkage. Two extended families of GSDs having PAA were assembled and used to determine the pattern of transmission. The results of this indicate that PAA is an autosomal recessive disease. The multiplexed MSS-1 was used to conduct an initial whole genome screen, although no markers were suggestive of linkage.
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Defeitos congênitos diagnosticados em ruminantes na região Sul do Rio Grande do Sul / Congenital defects in ruminants in Southern BrazilPEREIRA, Clairton Marcolongo 22 February 2010 (has links)
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Previous issue date: 2010-02-22 / Congenital defects and hereditary diseases in cattle, sheep and buffaloes were studied through a review of necropsy files of the Laboratório Regional de Diagnóstico (LRD) of the Faculdade of Veterinária of the Universidade Federal de Pelotas (UFPel) between 1978 and 2009. The occurrence of congenital defects and/or hereditary diseases in cattle, sheep and buffaloes were 0.89%, 0.36% e 7.55% respectively from all received material. The defects were classified according the affected system. From 48 of congenital defects and/or hereditary diseases observed in cattle 21 (43.75%) affected the skeletal system (chondrodysplasia, scoliosis, lateral deviation of mandible, palatoschisis and unclassified malformation) nine (18.75%) the central nervous system (hypoplasia of olfatory and frontal lobes, cerebellar cortical degeneration, spina bifida, congenital hypomielinogenesis, hereditary hypermetria, cerebellar hypoplasia and pachygiria), nine (18.75%) the muscular system (arthrogryposis), three (6.25%) the cardiovascular system (patent ductus arteriosus and unclassified malformation), one (2.08%) the lymphatic system (hereditary lymphatic hypoplasia), one (2.08%) o alimentary system (atresia ani) and one (2.08%) the eye (congenital cataract). In five cases (10.42%) different systems were affected (diprosopus and decephalus dipos dibraqius). In sheep all observed defects affected various systems (anomalous twins and aprosopia). Of eight cases of congenital defects/hereditary diseases diagnosed in buffaloes three (37.5%) affected the muscular system (arthrogriposis and double muscle), two (25%) the integument (mechanobullous dermatosis and albinism), one (12.5%) the central nervous system (hydranencephaly), one (12.5%) the central nervous system/ integument (hydranencephaly/albinism) and one (12.5%) the alimentary system (megaesofagus). It was concluded that the sporadic congenital defects cause little economical losses in cattle. Environmental congenital defects can cause losses in certain localized geographic areas or farms. The hereditary diseases were important by mortality of animals and by spread of undesirable genes in cattle breeding from milk production region in Southern Brazil. In sheep the congenital defects are rare. In water buffaloes the high prevalence of hereditary diseases was a consequence of the high consanguinity of herd and management measures need to be taken to avoid the spread of recessive genes that are difficult to control. / Foi realizado um estudo das malformações congênitas/doenças hereditárias diagnosticadas em bovinos, ovinos e bubalinos através da revisão dos protocolos de necropsia do Laboratório Regional de Diagnóstico (LRD) da Faculdade de Veterinária da Universidade Federal de Pelotas (UFPel) entre 1978 e 2009. A ocorrência de defeitos congênitos e/ou doenças hereditárias em bovinos, ovinos e bubalinos representou 0,89%, 0,36% e 7,55% respectivamente, de todos os materiais dessas espécies recebidos. Os defeitos foram classificados de acordo com o sistema afetado. Dos 48 casos de defeitos congênitos e/ou doenças hereditárias diagnosticados em bovinos 21 (43,75%) afetaram o sistema esquelético (condrodisplasia, escoliose, desvio lateral da mandíbula, fenda palatina e malformação não classificada) nove (18,75%) o sistema nervoso central (hipoplasia dos lobos frontais e olfatórios, degeneração cerebelar cortical, espinha bífida, hipomielinogênese congênita, hipermetria hereditária, hipoplasia cerebelar e paquigiria), nove (18,75%) o sistema muscular (artrogripose), três (6,25%) o sistema cardiovascular (persistência do ducto arterioso e malformação não classificada), um (2,08%) o sistema linfático (hipoplasia linfática), um (2,08%) o sistema gastrintestinal (atresia anal) e um (2,08%) o olho (catarata congênita). Em cinco casos (10,42%) vários sistemas estavam afetados (diprosopo e dicéfalo dipos dibráquio). Todos os casos de defeitos congênitos observados em ovinos (gêmeos anômalos e aprosopia) afetaram vários sistemas. Dos oito casos de defeitos congênitos e/ou doenças hereditárias diagnosticados em búfalos três (37,5%) afetaram o sistema muscular (artrogripose e hiperplasia muscular), dois (25%) o sistema tegumentar (dermatose mecânico-bolhosa e albinismo), um (12,5%) o sistema nervoso central (hidranencefalia), um (12,5%) o sistema nervoso central/tegumentar/fotorreceptor (hidranencefalia/albinismo), e um (12,5%) o sistema gastrintestinal (megaesôfago). Concluiu-se que os defeitos congênitos esporádicos têm pouca importância em bovinos. Defeitos congênitos de causas ambientais podem trazer prejuízos econômicos importantes em determinadas regiões ou estabelecimentos. As doenças comprovadamente hereditárias são importantes não só pela mortalidade mas, também, pela possibilidade de disseminação de genes indesejáveis nas diferentes raças, principalmente aquelas criadas em pequenas propriedades rurais da bacia leiteira da região. Em ovinos os defeitos congênitos são raros. Em bubalinos a alta frequência de doenças hereditárias na raça Murrah foi atribuída a alta consanguinidade do rebanho e medidas de controle devem ser tomadas para evitar-se a contínua disseminação, principalmente dos genes recessivos que são mais difíceis de controlar.
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Microcomputer-assisted diagnosis of inherited disorders of the skeletonVan Greunen, Francois 25 July 2017 (has links)
Several hundred inherited disorders of the skeleton have been delineated. Individually these conditions are rare, but as a group they cause much crippling and hardship. Several factors, including the rarity and complexity of the manifestations of these conditions, as well as semantic overlap, impede the accurate diagnosis which is essential for effective treatment. In this regard, the adoption of microcomputers warrants evaluation as a high technology aid. Microcomputers have developed tremendous capabilities during recent years. The state of the art has become such that a diagnostic aid facility on such a device has been demonstrated in various disciplines of medicine and may also be feasible in the area of inherited skeletal disorders. The study which forms the basis of this thesis, concerns the investigation of this feasibility and has led to the development of an effective working model which sets the basis for microcomputer-aided diagnosis. The design features followed in this project are similar to those conventionally employed for "Expert systems" on mainframe computers. A comprehensive knowledge base consisting of over 200 skeletal disorders and 700 radiographic and clinical manifestations, has resulted. Furthermore, the application is capable of "learning", although inference as employed by the inference engines of real expert systems, is not employed. In this context learning implies that the knowledge base, with the passage of time, improves considerably when used by experts. Serendipitous findings in this regard are: • 1) Considerable improvement of existing profile descriptions can occur without any increased demands on computer memory and storage space; • 2) Growth of the knowledge base in the form of additional disease profiles can be effected with very modest inroads on memory and storage resources. The computerized diagnostic aid which resulted from this thesis, has been demonstrated to be successful in both the Department of Human Genetics of the University of Cape Town and the Department of Paediatrics of the Johannes Gutenberg University in Mainz. Evaluated both in terms of efficiency and utility, the system provides an enhancement to the specialist genetic diagnostician. These achievements have been effected by means of a unique newly developed application of compressed bit-mapping, attained by writing the applicable programs in Turbo Pascal and 8086- assembler languages. Calculations indicate that much larger data bases may possibly be implemented on present-day microcomputers by means of the methods developed in this project.
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Genetinių ligų ir ydų paplitimas atskirose kačių veislėse / The prevalence of genetic diseases and vices in different cat breedsKovalenkienė, Julija 05 March 2014 (has links)
Daugelis kačių veislių yra imlios įvairioms ligoms ir patologijoms. Kai kurios iš šių mutacijų nėra pavojingos kačių sveikatai, kitos sukelia sunkias ligas, trečios yra veislės požymis.
Genetinės ligos ir ydos skirstomos į fenokopijas, dizgenetines anomalijas ir įgimtas ligas ir ydas. Dažniausiai paplitusios genetinės ligos tarp atskirų kačių veislių yra šios: hipertrofinė kardiomiopatija (HCM), inkstų policistozė (PKD), progresuojanti tinklainės atrofija (rdAc-PRA), gangliozidozė (GM1, GM2), piruvato kinazės trūkumas (PK), glikogeno kaupimosi liga IV tipo (GSD-IV), stuburo raumenų atrofija (SMA). Ydos: plokščios krūtinės kačiukų sindromas, bambinė išvarža, įgimta veido kaulų anomalija, Vandenburgo sindromas, polidaktilija, ektrodaktilija, sindaktilija, nesuaugęs kietasis gomurys, kriptorchizmas.
Genetiniam tyrimui atlikti imamas mėginys iš katės skruosto vidinės pusės (reikalingos žando ląstelės) tamponėlio pagalba. Paėmus mėginį, tamponai įdedami į specialų voką su užpildytų blanku ir siunčiami paštu į laboratoriją. Laboratorijoje, atliekant genetinius tyrimus, naudojama DNR polimerazės grandinės reakcija bei genų sukibimo metodas. Genetinį tyrimą galima atlikti bet kurio amžiaus gyvūnui.
Nustatėme, kad Lietuvoje per 2009-2013 metus mano tirtose veterinarijos klinikose daugiausia diagnozuota inkstų policistozės, kriptorchizmo, aklumo, bambinės išvaržos ir kurtumo atvejų. Iš kačių genetinių ligų Lietuvoje dažniausiai pasitaiko tik inkstų policistozė ir hipertrofinė... [toliau žr. visą tekstą] / Many cat breeds are susceptible to various diseases and pathologies. Some of these mutations are not dangerous to the health of cats, others cause severe diseases, third ones, are the feature of breed.
Genetic diseases and vices are divided into phenocopies, dysgenetic anomalies, and congenital diseases and defects. Most prevalent genetic diseases among different cat breeds are: hipertrophic cardiomyopathy (HCM), polycystic kidney disease (PKD), progressive retinal atrophy (rdAc-PRA), gangliosidosis (GM1, GM2), pyruvatkinase deficiency (PK), glycogen storage disease IV type (GSD-IV), spinal muscular atrophy (SMA). Vices: flat chest kitten syndrome, umbilical hernia, congenital abnormality of the facial bones, Vandenburg‘s syndrome, polydactyly, ectrodactyly, syndactyly, cleft hard palate, cryptorchidism.
Use brushes to collected cells from inside the cheek (buccal cells). Place all sample containing sample brushes and completed submission forms into a suitable envelope and male to laboratory. During the genetic research, laboratories are refering to the DNA polymerase chain reaction and gene bonding method. Genetic testing can be performed to the animal of any age.
We found out, that in Lithuania in the years of 2009-2013, in veterinary clinics, where I did my research, the following diseases were diagnosed the most: kidney polycystosis, cryptorchidism, blindness, deafness and umbilical hernia. Among feline genetic diseases, only kidney polycystosis and hypertrophic... [to full text]
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Aconselhamento genetico e prevenção da cegueira : percepção e conduta de oftalmologistas e pacientes portadores de deficiencia visual / Genetic counseling and prevetion of blindness : perception and conduct of brazilian ophtalmologists and patients with visual impairementRim, Priscila Hae Hyun, 1960- 12 June 2006 (has links)
Orientadores: Antonio Sergio Ramalho, Luis Alberto Magna / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-08T02:28:10Z (GMT). No. of bitstreams: 1
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Previous issue date: 2006 / Resumo: O presente trabalho tem por objetivos verificar a percepção de oftalmologistas brasileiros em relação à contribuição da Genética em sua atuação médica rotineira e a conduta frente a portadores de doenças hereditárias; investigar o nível de conhecimento e a conduta desses pacientes a respeito de sua condição e verificar a contribuição do aconselhamento genético na vida destes pacientes. Duzentos oftalmologistas que atuam na região de Campinas, SP, Brasil (universidades e/ou clínicas particulares) foram convidados a participar, por via postal, de uma entrevista sobre os seus conhecimentos, práticas e opiniões no campo da genética. A casuística de pacientes foi constituída por 53 portadores de deficiência visual importante (acuidade visual com a melhor correção menor que 0,3), de provável etiologia genética, entrevistados em um hospital universitário no período de 18 meses. O conteúdo da entrevista consistiu de perguntas sobre seus conhecimentos, opiniões, condutas e a situação ocular relativos à sua condição, utilizando-se de questionários de múltipla escolha, que permitiram a análise estatística, com comparação de proporções e testes de associação. Examinou-se também uma amostra-controle, constituída por 142 irmãos normais de pacientes, para comparação de alguns indicadores de integração social, principalmente o estabelecimento de parcerias conjugais estáveis e reprodução. Dentre os 73 profissionais que responderam o questionário (36%), foram constatadas altas taxas (49% a 88%) de respostas positivas sobre os seus conhecimentos básicos de genética, porém baixas taxas (10% a 33%) de utilização desses conhecimentos na rotina clínica. Apenas 45% dos indivíduos com oftalmopatias hereditárias receberam aconselhamento genético, geralmente fornecido pelo próprio oftalmologista. O encaminhamento a serviço de genética foi observado em 25% dos casos. O aconselhamento genético foi uma das variáveis que, juntamente com o sexo feminino e o maior nível educacional, mostraram-se associadas a mudanças no planejamento familiar. Embora os pacientes tenham revelado maior dificuldade no estabelecimento de vínculos reprodutivos estáveis, eles tiveram filhos na mesma proporção que os seus irmãos sem a deficiência visual, o que reforça a importância do aconselhamento genético. O potencial terapêutico e preventivo do aconselhamento genético não está sendo explorado adequadamente na prevenção da cegueira. A genética merece ser discutida de forma menos teórica e mais pragmática, não somente entre os oftalmologistas, mas entre os médicos e a população em geral, sobre a aplicação do potencial da genética em benefício dos pacientes, por meio de um aconselhamento genético abrangente, direcionado para a comunidade / Abstract: This study verified the perception and behavior of Brazilian ophthalmologists in relation to hereditary eye diseases and the contribuition of Genetics in their routine practice; and verified the perception and behavior of patients with severe visual impairment and the contribuition of genetic counseling in their lives. Invitations were posted to 200 ophthalmologists, who practice in the area of Campinas, SP, Brazil, to participate in an interview concerning their knowlegde, behavior and opinions in the field of Genetics. Patients sample was composed of 53 individuals with severe visual impairment (visual acuity of less than 0.3 in the better eye with the best correction) caused by genetic factors. The interviews were held in a university hospital over a period of 18 months. The multiple-choice questionnaire applied permitted statistical analysis, for proportion comparisons and associative tests. A control sample composed of 142 normal patients siblings was also examined to compare some social integration indicators - mainly the establishment of stable couples and reproduction. Of the 73 professionals who answered the questionnaire (36%), the percentage of affirmative responses regarding basic genetic knowledge was high (49% to 88%) but the application of this knowledge to regular clinical routine was poor (10% to 33%). Only 45% of the individuals with hereditary ophthalmopathies received genetic counseling, which was usually offered by the ophthalmologist. Referrals to the genetic service consisted of 25% of the cases. The variable genetic couseling, together with others such as female sex and those having a higher educational level, significantly influenced alterations in family planning. Although they had poor access to the establishment of stable conjugal unions, they had children in the same proportion as their normal siblings. This fact underscores the importance of genetic counseling. The therapeutic and preventive potential of genetic counseling in the prevention of blindness is not adequately used. Discussions on genetics held with Brazilian ophthalmologists and the community about the use of this potential, for the benefit of patients, through genetic counseling, should be more pragmatic and less theoretical / Mestrado / Oftalmologia / Mestre em Ciências Médicas
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Testování mutací genů v asociasci k některým významným dědičným onemocněním u border kolieKREJČOVÁ, Lenka January 2018 (has links)
This diploma thesis summarizes knowledge of significant genetically contitioned deseases occurring in border collies. There is described a total of 14 diseases, some with the location of causal mutation not yet known. Primary focus of this thesis is g.4411956_4411960delGTTT mutation of gene VPS13B causing Trapped Neuthrophil Syndrome (TNS), MDR1 gene's mutation AF045016.1: c.227_230delATAG associated with multidrug resistance (MDR1) and CUBN gene's mutation c.8392delC which causes intestinal malabsorption of cobalamin by another name ImerslundGräsbeck syndrome (IGS). A genotype analysis of 89 border collies with a proof of origin was performed. The DNA was extracted from buccal mucosal swabs, the isolation of DNA was performed by Chelex-100 from the native material. The analysis was proceeded by optimized PCR-RFLP method using restrictive MboI (MDR1) and Msl I (IGS) enzymes. There were detected 4 g.4411956_4411960delGTTT mutation vectors causing TNS. As for the MDR1 and IGS there wasn't detected any affected case.
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