DOCSLIB.ORG

(Synpolydactyly). 1 Field Investigation, Clinical and Pedigree Data J Med Genet: First Published As 10.1136/Jmg.32.6.421 on 1 June 1995

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(Synpolydactyly). 1 Field Investigation, Clinical and Pedigree Data J Med Genet: First Published As 10.1136/Jmg.32.6.421 on 1 June 1995 JMed Genet 1995;32:421-434 421 A large Turkish kindred with syndactyly type II (synpolydactyly). 1 Field investigation, clinical and pedigree data J Med Genet: first published as 10.1136/jmg.32.6.421 on 1 June 1995. Downloaded from Bekir Sitki Sayli, A Nurten Akarsu, Ugur Sayli, Okan Akhan, Serdar Ceylaner, Mansoor Sarfarazi Abstract reported.3 The different anatomical types of A very large Turkish family with syn- isolated syndactyly and polydactyly have been dactyly type II (synpolydactyly (SPD)) is presented clearly by Temtamy and McKusick.' described, which originated from and is However, the clinical expression of various mainly concentrated in the village of Der- types of syndactyly may be more complicated, bent, Afyon. The kindred consists of 425 causing difficulties in proper classification. Fur- subjects over seven generations, of whom thermore, an alternative classification of the 182 are affected. It appears that a founder syndactylies and polydactylies has recently been effect in this village has led to this extensive proposed, based mainly on whether pattern kindred. This condition is inherited as an formation is normal or abnormal, and whether autosomal dominant trait with variable secondary modelling of the limb bud appears expressivity and an estimated penetrance to be defective.4 of 96%. Penetrance is different between In some cases, syndactyly and polydactyly are the upper (96%) and lower (69.5%) ex- found together. This is the case with syndactyly tremities. No excess of affected males or type II (synpolydactyly (SPD)), in which the females or other associated features were third and fourth fingers as well as the fourth documented in this condition. Variations and fifth toes show syndactyly. This is usually in the involvement of one or both hands, associated with partial or complete re- upper or lower extremities, bone and soft duplication of the same fingers and fifth toe.' tissue, as well as variation in the affected We describe here a very large and interesting Department of subjects of two successive generations Turkish kindred with SPD affecting 182 sub- Medical Biology were documented. We also noted that me- jects, which originated from and is mainly con- and Genetics, The University of Ankara, tacarpal and metatarsal involvement and centrated in the village of Derbent, Afyon. Faculty of Medicine, middle phalangeal hypoplasia of the feet kindred spans at least 140 years and seven Sihhiye, Ankara, are the consistent features of SPD and, generations. http://jmg.bmj.com/ Turkey should be considered as char- B S Sayli therefore, A N Akarsu acteristic of this phenotype. We observed four different phenotypes in various Materials and methods Orthopedics Clinic, branches of the Derbent kindred: (1) sub- DESCRIPTION OF THE AREA Etimesgut Community Hospital, Ankara, jects presenting typical features of SPD; Derbent is a village in Bayat County, Afyon, Turkey (2) subjects exhibiting both pre- and post- an old mid-Anotolian city (fig 1) which is U Sayli axial polydactyly simultaneously; (3) per- located about 8 km from Bayat on the Ankara- on October 1, 2021 by guest. Protected copyright. Department of sons manifesting postaxial polydactyly Afyon highway. It is not known when the village Radiology, University type A; and (4) subjects born to two affec- was established, but nearby ruins indicate that of Hacettepe, Faculty ted parents with severe hand and foot de- it is old. It was neglected over time and its of Medicine, Sihhiye, Ankara, Turkey formities that have not been previously inhabitants became impoverished. The village O Akhan described in any other SPD families (that is inhabited by 1024 people in 107 dwellings is, homozygotes). A total of 27 affected in three quarters (Bayat Health Center Report, Department of Medical Biology offspring were born to two such affected 1992). The population is mainly engaged in and Genetics, parents, ofwhom seven are expected to be classical agriculture and husbandry. According University of homozygous for the SPD gene. This group to some of the elderly villagers, a woman from Erciyes, Faculty of Medicine, is presented in an accompanying paper in a neighbouring village who had come to Der- Kayseri, Turkey this issue oftheJournal. A molecular study bent as a bride brought with her this "unique S Ceylaner is currently under way to identify the chro- hand and foot abnormality". However, there mosomal location of the defective gene. Surgical Research are several villages named Derbent in the Centre, Department of middle county, and no-one remembers the Surgery, University (7Med Genet 1995;32:421-434) of Connecticut Health Centre, Farmington, Table 1 The relationship between the circular pedigree Connecticut and sub-pedigrees 06030-1110, USA Syndactyly as an isolated entity is classified in A N Akarsu several ways, simple, complete, cutaneous, and Family No Pedigree PID No Circular PID No M Sarfarazi osseous.' Polydactyly, another congenital mal- SPD-1 2 III-4 Correspondence to: formation of the hands and feet, generally ap- SPD-2 1 II2 Dr Sarfarazi. SPD-3 1 II-3 pears preaxial or postaxial to the limb.2 1 Received 9 August 1994 SPD-4 or 2 I-2 Symmetrical or bilateral involvement, as in the SPD-5 1 II1 18 Revised version accepted for SPD-6 1 or 2 II19 publication 5 January 1995 involvement of all four limbs, has also been 422 Sayli, Akarsu, Sayli, Akhan, Ceylaner, Sarfarazi BLACK SEA C.I.S. J Med Genet: first published as 10.1136/jmg.32.6.421 on 1 June 1995. Downloaded from *ANKARA BAYAT 0 AFYONO Derbent IRAQ MEDITERRANEAN SEA SCALE N 0 80 160 240 320 40( i$V77 I , A ir km 1: 6,800,000 S Figure 1 Map of Turkey showing the origin of the synpolydactyly gene in the village of Derbent and its spread to the neighbouring areas (inset map). Distances are shown on the scale bar. woman's name or when she arrived. As can The genealogy has been traced back to four be predicted from the pedigree (fig 2), this subjects in a single generation, but as yet we http://jmg.bmj.com/ condition had to have occurred at least 140 to have not been able to confirm that the SPD 150 years ago. Despite its longstanding pres- phenotype originated from a single person. The ence, neither medical practitioners nor laymen circular pedigree was constructed as a pictorial (including politicians) have ever paid attention representation of all pedigrees combined (fig to the condition. Surgery was performed on 2). Details of the findings on physical ex- one person's hand many years ago, with no amination are summarised on each individual further interest being shown. This village and sub-pedigree (fig 3A-F). The heterozygotes in the affected inhabitants have come to public these pedigrees are shown as half shaded and on October 1, 2021 by guest. Protected copyright. attention through a television programme, the homozygotes as fully shaded symbols. The making this study urgent and feasible. sub-pedigrees were constructed by deduction from the circular pedigree. The common per- sonal identification numbers (PID) between FIELD INVESTIGATION the circular and sub-pedigrees are shown in An extensive study was planned by a team of table 1. physicians (including the authors) following the Physical examinations were carried out with first visit to Derbent. Affected and unaffected emphasis on the details of the hand and foot subjects were interviewed either in their homes malformations. X ray films were obtained at a or in a mutually convenient central location. nearby centre. Some subjects were asked to go Pedigrees were constructed by repeatedly to Ankara for thorough evaluation and ortho- checking and reviewing all records related to paedic management. So far, routine labora- births and deaths from the year 1906 onwards. tory tests have been done only on those subjects Table 2 Distibution of subjects in the Derbent kindred Status Living Dead Total M F Sum M F Sum M F Sum Affected 72 77 149 18 15 33 90 92 182 Normal 63 75 138 11 6 17 74 81 155 Sums 135 152 287 29 21 50 164 173 337 Unknowns 0 0 0 8 6 14 8 6 14 Spouses 19 19 38 19 17 36 38 36 74 Totals 154 171 325 56 44 100 210 215 425 A large Turkish kindred with syndactyly type II (synpolydactyly). 1 Field investigation, clinical and pedigree data 423 J Med Genet: first published as 10.1136/jmg.32.6.421 on 1 June 1995. Downloaded from http://jmg.bmj.com/ on October 1, 2021 by guest. Protected copyright. * * Syndactyly type 11 v Q Sterile marriage Figure 2 The circular representation of the Derbent pedigree. The proband is shown by an arrow. In order to simplify the pedigree, we have shown all the people with various types of SPD by solid symbols, unaffected people by open symbols and have shown only the children of affected subjects and not those of the normal subjects. Details of this kindred are presented in each individual sub-pedigree (fig 3 A-F). visiting Ankara, and corrective operations have to discriminate the following four major groups been planned or performed on a number of ofmalformations in the same kindred: (1) those them. presenting typical features of the SPD pheno- type; (2) those showing both pre- and postaxial Results SPD simultaneously; (3) those having postaxial There are 182 people affected with the SPD polydactyly type A; and (4) those with bilateral, phenotype, of whom 33 have now died (table complete, complex SPD (that is, probable 2). There are no written records of their mal- homozygotes). The distribution of subjects in formations, but they were accurately described these groups is shown in table 3. by family members. We examined 106 subjects In this paper, a clinical description of the and obtained x rays from 41 affected people first three groups will be presented.
Load more

Recommended publications
  • Type II Familial Synpolydactyly: Report on Two Families with an Emphasis on Variations of Expression
    European Journal of Human Genetics (2011) 19, 112–114 & 2011 Macmillan Publishers Limited All rights reserved 1018-4813/11 www.nature.com/ejhg SHORT REPORT Type II familial synpolydactyly: report on two families with an emphasis on variations of expression Mohammad M Al-Qattan*,1 Type II familial synpolydactyly is rare and is known to have variable expression. However, no previous papers have attempted to review these variations. The aim of this paper was to review these variations and show several of these variable expressions in two families. The classic features of type II familial synpolydactyly are bilateral synpolydactyly of the third web spaces of the hands and bilateral synpolydactyly of the fourth web spaces of the feet. Several members of the two families reported in this paper showed the following variations: the third web spaces of the hands showing syndactyly without the polydactyly, normal feet, concurrent polydactyly of the little finger, concurrent clinodactyly of the little finger and the ‘homozygous’ phenotype. It was concluded that variable expressions of type II familial synpolydactyly are common and awareness of such variations is important to clinicians. European Journal of Human Genetics (2011) 19, 112–114; doi:10.1038/ejhg.2010.127; published online 18 August 2010 Keywords: type II familial syndactyly; inherited synpolydactyly; variations of expression INTRODUCTION CASE REPORTS Type II familial synpolydactyly is rare and it has been reported in o30 The first family families.1–12 It is characterized by bilateral synpolydactyly of the third The family had a history of synpolydactyly type II for several web spaces of the hands and bilateral synpolydactyly of the fourth web generations on the mother’s side (Table 1).
    [Show full text]
  • The Genetic Basis for Skeletal Diseases
    insight review articles The genetic basis for skeletal diseases Elazar Zelzer & Bjorn R. Olsen Harvard Medical School, Department of Cell Biology, 240 Longwood Avenue, Boston, Massachusetts 02115, USA (e-mail: [email protected]) We walk, run, work and play, paying little attention to our bones, their joints and their muscle connections, because the system works. Evolution has refined robust genetic mechanisms for skeletal development and growth that are able to direct the formation of a complex, yet wonderfully adaptable organ system. How is it done? Recent studies of rare genetic diseases have identified many of the critical transcription factors and signalling pathways specifying the normal development of bones, confirming the wisdom of William Harvey when he said: “nature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows traces of her workings apart from the beaten path”. enetic studies of diseases that affect skeletal differentiation to cartilage cells (chondrocytes) or bone cells development and growth are providing (osteoblasts) within the condensations. Subsequent growth invaluable insights into the roles not only of during the organogenesis phase generates cartilage models individual genes, but also of entire (anlagen) of future bones (as in limb bones) or membranous developmental pathways. Different mutations bones (as in the cranial vault) (Fig. 1). The cartilage anlagen Gin the same gene may result in a range of abnormalities, are replaced by bone and marrow in a process called endo- and disease ‘families’ are frequently caused by mutations in chondral ossification. Finally, a process of growth and components of the same pathway.
    [Show full text]
  • Genetics of Congenital Hand Anomalies
    G. C. Schwabe1 S. Mundlos2 Genetics of Congenital Hand Anomalies Die Genetik angeborener Handfehlbildungen Original Article Abstract Zusammenfassung Congenital limb malformations exhibit a wide spectrum of phe- Angeborene Handfehlbildungen sind durch ein breites Spektrum notypic manifestations and may occur as an isolated malforma- an phänotypischen Manifestationen gekennzeichnet. Sie treten tion and as part of a syndrome. They are individually rare, but als isolierte Malformation oder als Teil verschiedener Syndrome due to their overall frequency and severity they are of clinical auf. Die einzelnen Formen kongenitaler Handfehlbildungen sind relevance. In recent years, increasing knowledge of the molecu- selten, besitzen aber aufgrund ihrer Häufigkeit insgesamt und lar basis of embryonic development has significantly enhanced der hohen Belastung für Betroffene erhebliche klinische Rele- our understanding of congenital limb malformations. In addi- vanz. Die fortschreitende Erkenntnis über die molekularen Me- tion, genetic studies have revealed the molecular basis of an in- chanismen der Embryonalentwicklung haben in den letzten Jah- creasing number of conditions with primary or secondary limb ren wesentlich dazu beigetragen, die genetischen Ursachen kon- involvement. The molecular findings have led to a regrouping of genitaler Malformationen besser zu verstehen. Der hohe Grad an malformations in genetic terms. However, the establishment of phänotypischer Variabilität kongenitaler Handfehlbildungen er- precise genotype-phenotype correlations for limb malforma- schwert jedoch eine Etablierung präziser Genotyp-Phänotyp- tions is difficult due to the high degree of phenotypic variability. Korrelationen. In diesem Übersichtsartikel präsentieren wir das We present an overview of congenital limb malformations based Spektrum kongenitaler Malformationen, basierend auf einer ent- 85 on an anatomic and genetic concept reflecting recent molecular wicklungsbiologischen, anatomischen und genetischen Klassifi- and developmental insights.
    [Show full text]
  • Angeborene Fehlbildungen Der Extremitäten
    Aus der Klinik für Orthopädie (Direktor: Prof. Dr. med. J. Hassenpflug) der Medizinischen Fakultät der Christian-Albrechts-Universität zu Kiel Die angeborenen Fehlbildungen der oberen und unteren Extremitäten in der Orthopädischen Universitätsklinik Kiel von 1974-2001 Inauguraldissertation zur Erlangung der Doktorwürde vorgelegt von Karsten Naused aus Wolfenbüttel Kiel 2014 1. Berichterstatter: Prof. Dr. J. Hassenpflug, Klinik für Orthopädie 2. Berichterstatter: Prof. Dr. M. Schrappe, Klinik für Allgemeine Pädiatrie Tag der mündlichen Prüfung: 12.06.2014 Zum Druck genehmigt, Kiel, den 12.06.2014 gez.: PD Dr. S. Lippross, Klinik Unfallchirurgie (Prüfer) Prof. Dr. A. Seekamp, Klinik Unfallchirurgie (Beisitzer) Prof. Dr. Johann Roider, Vorsitzender des Ausschusses für Promotion Inhaltsverzeichnis 1. Einleitung Seite 1.1 Vorbemerkung.................................................................................................1 1.2 Historisches.....................................................................................................2 1.3 Embryologie.....................................................................................................3 1.4 Ätiologie und Pathogenese..............................................................................6 2. Patientengut und Methode 2.1 Quellen der Patientendaten...........................................................................10 2.2 Dokumentation der Daten..............................................................................12 2.3 Datenabfrage.................................................................................................13
    [Show full text]
  • Polydactyly of the Hand
    A Review Paper Polydactyly of the Hand Katherine C. Faust, MD, Tara Kimbrough, BS, Jean Evans Oakes, MD, J. Ollie Edmunds, MD, and Donald C. Faust, MD cleft lip/palate, and spina bifida. Thumb duplication occurs in Abstract 0.08 to 1.4 per 1000 live births and is more common in Ameri- Polydactyly is considered either the most or second can Indians and Asians than in other races.5,10 It occurs in a most (after syndactyly) common congenital hand ab- male-to-female ratio of 2.5 to 1 and is most often unilateral.5 normality. Polydactyly is not simply a duplication; the Postaxial polydactyly is predominant in black infants; it is most anatomy is abnormal with hypoplastic structures, ab- often inherited in an autosomal dominant fashion, if isolated, 1 normally contoured joints, and anomalous tendon and or in an autosomal recessive pattern, if syndromic. A prospec- ligament insertions. There are many ways to classify tive San Diego study of 11,161 newborns found postaxial type polydactyly, and surgical options range from simple B polydactyly in 1 per 531 live births (1 per 143 black infants, excision to complicated bone, ligament, and tendon 1 per 1339 white infants); 76% of cases were bilateral, and 3 realignments. The prevalence of polydactyly makes it 86% had a positive family history. In patients of non-African descent, it is associated with anomalies in other organs. Central important for orthopedic surgeons to understand the duplication is rare and often autosomal dominant.5,10 basic tenets of the abnormality. Genetics and Development As early as 1896, the heritability of polydactyly was noted.11 As olydactyly is the presence of extra digits.
    [Show full text]
  • Evolution of Morphology: Modifications to Size and Pattern
    Evolution of Morphology: Modifications to Size and Pattern The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Uygur, Aysu N. 2014. Evolution of Morphology: Modifications to Size and Pattern. Doctoral dissertation, Harvard University. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274611 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Evolution of Morphology: Modifications to Size and Pattern A dissertation presented by Aysu N. Uygur to The Division of Medical Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the subject of Genetics Harvard University Cambridge, Massachusetts May, 2014 iii © 2014 by Aysu N. Uygur All Rights Reserved iv Dissertation Advisor: Dr. Clifford J. Tabin Aysu N. Uygur Evolution of Morphology: Modifications to Size and Pattern Abstract A remarkable property of developing organisms is the consistency and robustness within the formation of the body plan. In many animals, morphological pattern formation is orchestrated by conserved signaling pathways, through a process of strict spatio-temporal regulation of cell fate specification. Although morphological patterns have been the focus of both classical and recent studies, little is known about how this robust process is modified throughout evolution to accomodate different morphological adaptations. In this dissertation, I first examine how morphological patterns are conserved throughout the enourmous diversity of size in animal kingdom.
    [Show full text]
  • Congenital Malformations in Sea Turtles: Puzzling Interplay Between Genes and Environment
    animals Review Congenital Malformations in Sea Turtles: Puzzling Interplay between Genes and Environment Rodolfo Martín-del-Campo 1, María Fernanda Calderón-Campuzano 2, Isaías Rojas-Lleonart 3, Raquel Briseño-Dueñas 2,4 and Alejandra García-Gasca 5,* 1 Department of Oral Health Sciences, Faculty of Dentistry, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; [email protected] 2 Marine Turtle Programme, Instituto de Ciencias del Mar y Limnología-UNAM-FONATUR, Mazatlán, Sinaloa 82040, Mexico; [email protected] (M.F.C.-C.); [email protected] (R.B.-D.) 3 Universidad Central “Martha Abreu” de las Villas (IRL), CUM Remedios, Villa Clara 52700, Cuba; [email protected] 4 Banco de Información sobre Tortugas Marinas (BITMAR), Unidad Académica Mazatlán, Instituto de Ciencias del Mar y Limnología-UNAM, Mazatlán, Sinaloa 82040, Mexico 5 Laboratory of Molecular and Cellular Biology, Centro de Investigación en Alimentación y Desarrollo, Mazatlán, Sinaloa 82112, Mexico * Correspondence: [email protected]; Tel.: +52-669-989-8700 Simple Summary: Congenital malformations can lead to embryonic mortality in many species, and sea turtles are no exception. Genetic and/or environmental alterations occur during early develop- ment in the embryo, and may produce aberrant phenotypes, many of which are incompatible with life. Causes of malformations are multifactorial; genetic factors may include mutations, chromosomal aberrations, and inbreeding effects, whereas non-genetic factors may include nutrition, hyperthermia, low moisture, radiation, and contamination. It is possible to monitor and control some of these Citation: Martín-del-Campo, R.; Calderón-Campuzano, M.F.; factors (such as temperature and humidity) in nesting beaches, and toxic compounds in feeding Rojas-Lleonart, I.; Briseño-Dueñas, R.; areas, which can be transferred to the embryo through their lipophilic properties.
    [Show full text]
  • Review Article Cleidocranial Dysplasia: Clinical and Molecular Genetics
    J Med Genet 1999;36:177–182 177 Review article Cleidocranial dysplasia: clinical and molecular genetics Stefan Mundlos Abstract Chinese named Arnold, was probably de- Cleidocranial dysplasia (CCD) (MIM scribed by Jackson.6 He was able to trace 356 119600) is an autosomal dominant skeletal members of this family of whom 70 were dysplasia characterised by abnormal aVected with the “Arnold Head”. CCD was clavicles, patent sutures and fontanelles, originally thought to involve only bones of supernumerary teeth, short stature, and a membranous origin. More recent and detailed variety of other skeletal changes. The dis- clinical investigations have shown that CCD is ease gene has been mapped to chromo- a generalised skeletal dysplasia aVecting not some 6p21 within a region containing only the clavicles and the skull but the entire CBFA1, a member of the runt family of skeleton. CCD was therefore considered to be transcription factors. Mutations in the a dysplasia rather than a dysostosis.7 Skeletal CBFA1 gene that presumably lead to syn- abnormalities commonly found include cla- thesis of an inactive gene product were vicular aplasia/hypoplasia, bell shaped thorax, identified in patients with CCD. The func- enlarged calvaria with frontal bossing and open tion of CBFA1 during skeletal develop- fontanelles, Wormian bones, brachydactyly ment was further elucidated by the with hypoplastic distal phalanges, hypoplasia of generation of mutated mice in which the the pelvis with widened symphysis pubis, Cbfa1 gene locus was targeted. Loss of one severe dental anomalies, and short stature. The Cbfa1 allele (+/-) leads to a phenotype very changes suggest that the gene responsible is not similar to human CCD, featuring hypo- only active during early development, as plasia of the clavicles and patent fonta- implied by changes in the shape or number of nelles.
    [Show full text]
  • 25. C:\Documents and Settings\Kwang-Il\My
    The human disease network Goh K-I, Cusick ME, Valle D, Childs B, Vidal M, Barabasi′ A-L (2007) Proc Natl Acad Sci USA 104:8685-8690 Disorder Class Bone Coats Cancer Urolithiasise Osteopetrosis disease NDP Caffey van_Buchem Exudative Cardiovascular disease disease vitreoretinopathy Norrie SLC34A1 disease 439 LRP5 Connective tissue disorder Nevo Hyperostosis, syndrome COL1A1 endosteal Dermatological PLOD1 217 PAX9 Oligodontia Osteogenesis Osteoporosis 1164 Developmental Ehlers-Danlos imperfecta syndrome Arthropathy COL3A1 Hypodontia Ear, Nose, Throat Aneurysm, COL1A2 familial_arterial Myasthenic Witkop 733 syndrome Heart syndrome Pseudoachondroplasia Endocrine 3-methylglutaconicaciduria OPA3 WISP3 Optic Marfan block MSX1 atrophy OPA1 Aortic syndrome Paramyotonia Sick_sinus Gastrointestinal aneurysm congenita syndrome 3558 Intervertebral_disc Brugada SCN4A disease syndrome Syndactyly Spondyloepiphyseal COMP COL9A2 Hematological Glaucoma Weill-Marchesani Shprintzen-Goldberg Cramps, SCN5A Zlotogora-Ogur Cleft dysplasia syndrome syndrome potassium-aggravated Myotonia 2785 syndrome palate Parkes_Weber Basal_cell FBN1 congenita Oculodentodigital COL9A3 1432 Immunological 1414 CYP1B1 syndrome nevus_syndrome MASS Hypokalemic Acquired dysplasia Peters long_QT_syndrome Epiphyseal FLNB RASA1 PTCH Keratitis syndrome periodic MATN3 Metabolic SHH anomaly Eye Ectopia Thyrotoxic paralysis dysplasia Atelosteogenesis anomalies Marshall Larson Capillary Basal_cell Holoprosencephaly Coloboma, periodic KCNH2 PVRL1 malformations GJA1 Incontinentia syndrome SLC26A2
    [Show full text]
  • Zur Morphologie Und Vererbung Des Polydaktylie-Luxations-Syndroms Bei Dem Wistar-Rattenstamm Shoe: WIST (Shoe)
    Tierärztliche Hochschule Hannover Zur Morphologie und Vererbung des Polydaktylie- Luxations-Syndroms bei dem Wistar-Rattenstamm Shoe:WIST(Shoe) INAUGURAL-DISSERTATION zur Erlangung des Grades einer Doktorin der Veterinärmedizin - Doctor medicinae veterinariae - (Dr. med. vet.) vorgelegt von Christine Krüger Hameln Hannover 2012 Wissenschaftliche Betreuung: Univ.-Prof. Dr. med. vet. Wolfgang Baumgärtner, Ph.D., Institut für Pathologie, Stiftung Tierärztliche Hochschule Hannover 1. Gutachter: Univ.-Prof. Dr. med. vet. Wolfgang Baumgärtner, Ph. D. 2. Gutachter: Univ.-Prof. Dr. med. vet. Michael Fehr Tag der mündlichen Prüfung: 29.11.2012 meinen Eltern 1 Einleitung ........................................................................................................... 1 2 Literaturübersicht ...............................................................................................3 2.1 Embryonale Gliedmaßenentwicklung ........................................................... 3 2.2 Gliedmaßenfehlbildungen des Menschen .................................................... 4 2.2.1 Klassifikation ......................................................................................... 4 2.2.2 Ätiologie ................................................................................................ 7 2.2.3 Häufigkeit ............................................................................................ 13 2.2.4 Fehlbildungen des Zeugo- und Autopodium beim Menschen ............. 14 2.2.4.1 Zeugopodium ..............................................................................
    [Show full text]
  • Triplet Repeat Diseases
    1 Triplet Repeat Diseases Stephan J. Guyenet and Albert R. La Spada University of Washington, Seattle, WA 98195 1 A Novel Mechanism of Genetic Mutation Emerges 3 1.1 Repeat Sequences of All Types and Sizes 3 1.2 Trinucleotide Repeat Expansion as a Cause of Disease: Unique Features Explain Unusual Genetics 4 2 Repeat Diseases and Their Classification 5 2.1 Summary of Repeat Diseases 5 2.2 Differences in Repeat Sequence Composition and Location within Gene 6 2.3 Classification Based upon Mechanism of Pathogenesis and Nature of Mutation 6 3 Type 1: The CAG/Polyglutamine Repeat Diseases 9 3.1 Spinal and Bulbar Muscular Atrophy 9 3.2 Huntington’s Disease 12 3.3 Dentatorubral Pallidoluysian Atrophy 15 3.4 Spinocerebellar Ataxia Type 1 16 3.5 Spinocerebellar Ataxia Type 2 18 3.6 Spinocerebellar Ataxia Type 3/Machado–Joseph Disease 19 3.7 Spinocerebellar Ataxia Type 6 21 3.8 Spinocerebellar Ataxia Type 7 22 3.9 Spinocerebellar Ataxia Type 17 25 3.10 Role of Aggregation in Polyglutamine Disease Pathogenesis 25 3.11 Protein Context 29 3.12 Transcriptional Dysregulation 30 3.13 Proteolytic Cleavage 30 4 Type 2: the Loss-of-function Repeat Diseases 33 4.1 Fragile X Syndrome 33 Encyclopedia of Molecular Cell Biology and Molecular Medicine, 2nd Edition. Volume 15 Edited by Robert A. Meyers. Copyright 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30652-8 2 Triplet Repeat Diseases 4.2 Fragile XE Mental Retardation 34 4.3 Friedreich’s Ataxia 36 4.4 Progressive Myoclonus Epilepsy Type 1 39 5 Type 3: the RNA Gain-of-function Repeat Diseases
    [Show full text]
  • REVIEW ARTICLE Genetic Disorders of the Skeleton: a Developmental Approach
    Am. J. Hum. Genet. 73:447–474, 2003 REVIEW ARTICLE Genetic Disorders of the Skeleton: A Developmental Approach Uwe Kornak and Stefan Mundlos Institute for Medical Genetics, Charite´ University Hospital, Campus Virchow, Berlin Although disorders of the skeleton are individually rare, they are of clinical relevance because of their overall frequency. Many attempts have been made in the past to identify disease groups in order to facilitate diagnosis and to draw conclusions about possible underlying pathomechanisms. Traditionally, skeletal disorders have been subdivided into dysostoses, defined as malformations of individual bones or groups of bones, and osteochondro- dysplasias, defined as developmental disorders of chondro-osseous tissue. In light of the recent advances in molecular genetics, however, many phenotypically similar skeletal diseases comprising the classical categories turned out not to be based on defects in common genes or physiological pathways. In this article, we present a classification based on a combination of molecular pathology and embryology, taking into account the importance of development for the understanding of bone diseases. Introduction grouping of conditions that have a common molecular origin but that have little in common clinically. For ex- Genetic disorders affecting the skeleton comprise a large ample, mutations in COL2A1 can result in such diverse group of clinically distinct and genetically heterogeneous conditions as lethal achondrogenesis type II and Stickler conditions. Clinical manifestations range from neonatal dysplasia, which is characterized by moderate growth lethality to only mild growth retardation. Although they retardation, arthropathy, and eye disease. It is now be- are individually rare, disorders of the skeleton are of coming increasingly clear that several distinct classifi- clinical relevance because of their overall frequency.
    [Show full text]