2009 Vienna - European Society of Human Genetics

More documents

Recommendations

Info

Molecular and biochemical basis of disease in common analysis) and in MYBPC3(novel). The patient group consisted of 16 individuals with a clinical diagnostic of HCM. DNA extraction was extracted from peripheral blood. All samples from the patient group were genotyped by MSG using a MassARRAY MALDI-TOF. The samples with no mutation found were scanned for novel mutations by HRM. All variants found were confirmed by automatic sequencing. The CSRP3 c.128delC mutation was found in heterozygoty in a 50-year old patient with diffused left ventricle hypertrophy. A novel mutation of the MYBPC3 was discovered in another HCM patient: c.C>T817/ p.Arg273Cys. Although still uncharacterized as disease-causing, affects a codon known to harbor a known HCM-causing mutation - p.Arg253His. This coupling of innovative techniques allowed the detection both of a known mutation on a seldom analyzed gene and a probably HCM-causing novel mutation. P16.28 Familial noncompaction cardiomyopathy: genetic and cardiologic features in adults and children Y. M. Hoedemaekers1 , K. Caliskan1 , M. Michels1 , I. Frohn - Mulder1 , J. van der Smagt2 , J. E. Phefferkorn1 , F. J. ten Cate1 , D. Dooijes1 , D. F. Majoor - Krakauer1 ; 1 2 Erasmus Medical Center, Rotterdam, The Netherlands, University Medical Center Utrecht, Utrecht, The Netherlands. Background: Noncompaction cardiomyopathy (NCCM) features a thickened bilayered left ventricular wall with a thin, compact epicardial layer and a thick endocardial layer with prominent intertrabecular recesses. NCCM is genetically heterogeneous. Similarly to hypertrophic (HCM) and dilated cardiomyopathy (DCM), NCCM has been associated with mutations in sarcomere genes. In order to contribute to a genetic classification for NCCM a systematic cardiologic family study was performed in a cohort of 56 consecutively diagnosed and molecularly screened patients with isolated NCCM (47 adults and nine children). Methods and Results: Cardiologic screening with electrocardiography, echocardiography and physical examination of 169 relatives from 46 unrelated NCCM probands revealed familial cardiomyopathy in 34 families (74%), including NCCM, HCM and DCM. Seventy-four percent of the relatives newly diagnosed with cardiomyopathy were asymptomatic, explaining that 54% of familial disease remained undetected by ascertainment of family history prior to cardiologic screening. The molecular screening included analysis of 17 genes yielding 29 different mutations in 23 probands (41%); 18 adult and five children. Fifteen single mutations and one double mutation on the same allele were transmitted in an autosomal dominant mode. Six adults and two children were compound or double heterozygous for two different mutations. In 19/34 (56%) of familial NCCM the genetic defect remained unknown. Conclusion: NCCM is predominantly a genetic disorder, requiring genetic counseling, DNA diagnostics and, also in absence of a genetic cause, cardiologic family screening. P16.29 takotsubo and congenital LQts in a patient with a novel mutation in the KCNH gene F. Fellmann 1 , E. Pruvot 2 , L. Sintra Grilo 3 , M. Grobéty 4 , V. Castella 5 , J. S. Beckmann 1,6 , H. Abriel 3 ; 1 Service of Medical Genetics, CHUV, Lausanne, Switzerland, 2 Service of Cardiology, CHUV, Lausanne, Switzerland, 3 Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland, 4 Clinique Cécil, Lausanne, Switzerland, 5 University Center of Legal Medicine, Lausanne, Switzerland, 6 Dept of Medical Genetics, UNIL, Lausanne, Switzerland. Delayed cardiac repolarization may be caused by inherited mutations in cardiac ion channel gene subunits (congenital long QT syndrome, LQTS) or secondary to cardiac pathologies, including the recently-described Takotsubo cardiomyopathy. We report the case of a female patient admitted at the emergency ward of the Lausanne university hospital because of a sudden convulsive syncopal event. The observation of a transient alteration of the ECG repolarization with a torsades de pointes episode 9 days after a surgical stress suggested a Takotsubo cardiomyopathy. After transient normalization of the ECG, congenital LQTS was diagnosed on the basis of a persistent QT prolongation. Genetic analyses identified a 7 amino-acid duplication (nc.343-363dup) located in the PAS domain of hERG1 N-terminus in the gene KCNH2 coding for the hERG1 channel. This mutation has not been reported yet. Three recent case reports suggested that both LQTS and Takotsubo syndrome may be causally related but no mutation in the LQTS genes have been identified yet.In conclusion, we describe a patient with Takotsubo uncovering a congenital form of LQTS. We show that LQTS is caused by an unusual KCNH2 mutation that has been characterized at the biophysical and biochemical levels. A putative causal relationship between LQTS and Takotsubo is discussed. However, the mechanisms underlying the link between the two disorders, if any, remain to be investigated. P16.30 Does δ-sarcoglycan-associated autosomal dominant cardiomyopathy exist? A. Sarkozy 1 , R. Bauer 1 , J. Hudson 1 , H. D. Müller 2 , C. Sommer 2 , G. Dekomien 3 , J. Bourke 4 , D. Routledge 1 , K. Bushby 1 , J. Klepper 5 , V. Straub 1 ; 1 Institute of Human Genetics, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom, 2 Department of Neuropathology, University of Mainz, Mainz, Germany, 3 Institute of Human Genetics, Ruhr- University Bochum,, Bochum, Germany, 4 Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom, 5 Department of Pediatrics, Klinikum Aschaffenburg, Aschaffenburg, Germany. The sarcoglycans are part of the dystrophin-glycoprotein-complex (DGC), an oligomeric complex spanning the plasma membrane of skeletal and cardiac muscle fibres. The sarcoglycan deficient limb girdle muscular dystrophies (LGMDs) are characterized by progressive weakness of the pelvic and shoulder girdle musculature and affected patients often develop a progressive and potentially fatal dilated cardiomyopathy (DCM). Dominant inheritance has not been reported in sarcoglycan-deficient LGMD. However, a previous report described autosomal dominant mutations in the δ-sarcoglycan (SGCD) gene in patients with familial and sporadic cases of DCM without significant skeletal muscle involvement. Here we clinically and genetically characterize a consanguineous family with a homozygous novel missense mutation (p.A131P) in the SGCD gene and a second δ-sarcoglycan mutation that has previously been reported to cause a fatal autosomal dominant DCM at young age. This second heterozygous mutation (p.S151A) was found in 4 heterozygous carriers for the A131P mutation, aged 3 to 64 years. Comprehensive clinical and cardiac investigation in all of the compound heterozygous family members revealed no signs of cardiomyopathy or LGMD. Even in the presence of a second disease causing mutation, the p.S151A mutation in the SGCD gene does not result in cardiomyopathy. This finding questions the pathological relevance of this sequence variant for causing familial autosomal dominant DCM and thereby the role of the SGCD gene in general as a disease causing gene for autosomal dominant DCM. P16.31 Blood pressure changes associated with eNOs gene polymorphism at patients with stress cardiomyopathy E. Kovaleva, E. Zemtsovskiy, V. Larionova; Pediatric Medical Academy, St.-Petersburg, Russian Federation. Objective: Possibility of pathological changes in myocardium caused by acute stress influence is well-known at this moment. At the same time chronic psychoemotional stress (PES) could be an independent reason of stress cardiomyopathy (SKMP) at the high-risk professional group’s person, which may have genetic markers of «low stress resistance», associated with vascular reactions caused by PES. We investigate blood pressure (BP) level and endothelial NO-synthase gene (eNOS) polymorphism at the persons exposed to chronic professional PES’ influence and also with noncoronarogenic heart’ damages. Design and methods. The subjects of research were railway’ engine-drivers: 58 men with SKMP diagnosed in case finding clinically significant arrhythmia and electrical conductivity disturbance at 24-h ECG monitoring and also non-ischemic repolarization abnormalities on ECG and/or ECG stress test. Exception criteria were coronary disease, arterial hypertension (above 140/90 mmHg), Primary/secondary cardiomyopathy other genesis, including inflammatory compared with 78 men without a cardiovascular pathology. All patients underwent clinical BP measurement and analysis for 4a/4b eNOS gene polymorphism by PCR. Results. The systolic (SBP) and diastolic (DBP) blood pressure levels at 4a (genotypes 4a/4b and 4a/4a) SKMP patients were signifi-
Molecular and biochemical basis of disease cant increased in comparison with 4b homozygous SKMP patients (123,07+8,3 vs 128,9+7,2 mm Hg, P
Page 1 and 2:
Volume 17 Supplement 2 May 2009 www
Page 3 and 4:
European Society of Human Genetics
Page 5 and 6:
Table of Contents spoken Presentati
Page 7 and 8:
Plenary Lectures PL2.2 massive para
Page 9 and 10:
Concurrent Symposia s01.1 Genome va
Page 11 and 12:
Concurrent Symposia Monogenic diabe
Page 13 and 14:
Concurrent Symposia invariable in t
Page 15 and 16:
Concurrent Symposia s11.2 clinical,
Page 17 and 18:
Concurrent Symposia s13.2 A novel g
Page 19 and 20:
Concurrent Sessions c01.1 mRNA-seq
Page 21 and 22:
Concurrent Sessions velopmental del
Page 23 and 24:
Concurrent Sessions development of
Page 25 and 26:
Concurrent Sessions c04.6 Duplicati
Page 27 and 28:
Concurrent Sessions genes to be rec
Page 29 and 30:
Concurrent Sessions c07.5 Prenatal
Page 31 and 32:
Concurrent Sessions with familial h
Page 33 and 34:
Concurrent Sessions University of W
Page 35 and 36:
Concurrent Sessions with this, we f
Page 37 and 38:
Concurrent Sessions had immotile ci
Page 39 and 40:
Concurrent Sessions abnormal glycos
Page 41 and 42:
Concurrent Sessions showers’ and
Page 43 and 44:
Concurrent Sessions partial gene de
Page 45 and 46:
Concurrent Sessions leads to distre
Page 47 and 48:
Genetic counseling Genetics educati
Page 49 and 50:
Page 51 and 52:
Page 53 and 54:
Page 55 and 56:
Page 57 and 58:
Page 59 and 60:
Clinical genetics and Dysmorphology
Page 61 and 62:
Page 63 and 64:
Page 65 and 66:
Page 67 and 68:
Page 69 and 70:
Page 71 and 72:
Page 73 and 74:
Page 75 and 76:
Page 77 and 78:
Page 79 and 80:
Page 81 and 82:
Page 83 and 84:
Page 85 and 86:
Page 87 and 88:
Page 89 and 90:
Page 91 and 92:
Page 93 and 94:
Page 95 and 96:
Page 97 and 98:
Page 99 and 100:
Page 101 and 102:
Page 103 and 104:
Page 105 and 106:
Cytogenetics P03. cytogenetics Recu
Page 107 and 108:
Cytogenetics use of metaphase analy
Page 109 and 110:
Cytogenetics 2: mother’s age < fa
Page 111 and 112:
Cytogenetics P03.028 HLA B27 allele
Page 113 and 114:
Cytogenetics karyotype revealed a p
Page 115 and 116:
Cytogenetics drome is estimated at
Page 117 and 118:
Cytogenetics P03.057 Pathological c
Page 119 and 120:
Cytogenetics grandmother and 2 mate
Page 121 and 122:
Cytogenetics method used to detect
Page 123 and 124:
Cytogenetics P03.082 High-resolutio
Page 125 and 126:
Cytogenetics All detected anomalies
Page 127 and 128:
Cytogenetics somy for chromosome 2.
Page 129 and 130:
Cytogenetics cially in chromosome 4
Page 131 and 132:
Cytogenetics (59.390.122 to 62.021.
Page 133 and 134:
Cytogenetics For further characteri
Page 135 and 136:
Cytogenetics 9p duplication. This c
Page 137 and 138:
Cytogenetics regions with mental /d
Page 139 and 140:
Cytogenetics donation program of po
Page 141 and 142:
Cytogenetics P03.165 interpretation
Page 143 and 144:
Cytogenetics P03.174 Deletion of th
Page 145 and 146:
Cytogenetics P03.183 An atypical 7q
Page 147 and 148:
Cytogenetics spermia, 11 oligosperm
Page 149 and 150:
Reproductive genetics and social fa
Page 151 and 152:
Reproductive genetics mosomal chang
Page 153 and 154:
Reproductive genetics two cohorts w
Page 155 and 156:
Reproductive genetics the 147 SC ch
Page 157 and 158:
Prenatal and perinatal genetics P05
Page 159 and 160:
Prenatal and perinatal genetics and
Page 161 and 162:
Prenatal and perinatal genetics fro
Page 163 and 164:
Prenatal and perinatal genetics dev
Page 165 and 166:
Prenatal and perinatal genetics in
Page 167 and 168:
Prenatal and perinatal genetics obj
Page 169 and 170:
Prenatal and perinatal genetics P05
Page 171 and 172:
Cancer genetics P06.005 tiling reso
Page 173 and 174:
Cancer genetics tient group in whic
Page 175 and 176:
Cancer genetics chronic inflammatio
Page 177 and 178:
Cancer genetics licular thyroid can
Page 179 and 180:
Cancer genetics also studied. In 31
Page 181 and 182:
Cancer genetics tile polyposis. We
Page 183 and 184:
Cancer genetics Upon recombinant ex
Page 185 and 186:
Cancer genetics variant allele was
Page 187 and 188:
Cancer genetics from patients with
Page 189 and 190:
Cancer genetics tion (PAX5 and GATA
Page 191 and 192:
Cancer genetics scribed underexpres
Page 193 and 194:
Cancer genetics of the ZIC gene fam
Page 195 and 196:
Cancer genetics Materials and metho
Page 197 and 198:
Cancer genetics the past and it is
Page 199 and 200:
Cancer genetics P06.130 spectrum an
Page 201 and 202:
Cancer genetics P06.139 the role of
Page 203 and 204:
Cancer genetics and MSH2 germline m
Page 205 and 206:
Cancer genetics P06.155 New roles f
Page 207 and 208:
Cancer genetics screening was perfo
Page 209 and 210:
Cancer genetics val (DFI) than pati
Page 211 and 212:
Cancer genetics is hTERC gene ampli
Page 213 and 214:
Cancer genetics on chromosome regio
Page 215 and 216:
Cancer genetics preferentially dupl
Page 217 and 218:
Cancer cytogenetics mutations in co
Page 219 and 220:
Cancer cytogenetics P07.08 molecula
Page 221 and 222:
Statistical genetics, includes Mapp
Page 223 and 224:
Page 225 and 226:
Page 227 and 228:
Page 229 and 230:
Page 231 and 232:
Page 233 and 234:
Page 235 and 236:
Complex traits and polygenic disord
Page 237 and 238:
Page 239 and 240:
Page 241 and 242:
Page 243 and 244:
Page 245 and 246:
Page 247 and 248:
Page 249 and 250:
Page 251 and 252:
Page 253 and 254:
Page 255 and 256:
Page 257 and 258:
Page 259 and 260:
Page 261 and 262:
Page 263 and 264:
Page 265 and 266:
Page 267 and 268:
Evolutionary and population genetic
Page 269 and 270:
Page 271 and 272:
Page 273 and 274:
Page 275 and 276:
Page 277 and 278:
Page 279 and 280:
Page 281 and 282:
Page 283 and 284:
Page 285 and 286:
Genomics, Genomic technology and Ep
Page 287 and 288:
Page 289 and 290:
Page 291 and 292:
Page 293 and 294:
Page 295 and 296:
Page 297 and 298:
Page 299 and 300:
Page 301 and 302:
Page 303 and 304:
Page 305 and 306:
Page 307 and 308:
Page 309 and 310:
Page 311 and 312:
Page 313 and 314:
Molecular basis of Mendelian disord
Page 315 and 316:
Page 317 and 318:
Page 319 and 320:
Page 321 and 322:
Page 323 and 324:
Page 325 and 326:
Page 327 and 328: Molecular basis of Mendelian disord
Page 351 and 352: Metabolic disorders P12.167 Pattern
Page 353 and 354: Metabolic disorders PKU. BH4 challe
Page 355 and 356: Metabolic disorders catepe Universi
Page 357 and 358: Metabolic disorders respectively. G
Page 359 and 360: Metabolic disorders enzymaticaly co
Page 361 and 362: Metabolic disorders Normal Affected
Page 363 and 364: Therapy for genetic disorders in th
Page 365 and 366: Therapy for genetic disorders P14.0
Page 367 and 368: Therapy for genetic disorders of me
Page 369 and 370: Laboratory and quality management P
Page 371 and 372: Laboratory and quality management T
Page 373 and 374: Molecular and biochemical basis of
Page 377: Molecular and biochemical basis of
Page 385 and 386: Genetic analysis, linkage ans assoc
Page 403 and 404: Author Index Allanson, J.: P02.140
Page 405 and 406: Author Index 0 Barbacioru, C.: C01.
Page 407 and 408: Author Index 0 Bonneau, D.: C16.2,
Page 409 and 410: Author Index 0 Chakravarti, A.: C13
Page 411 and 412: Author Index 0 Dan, D.: P01.39, P14
Page 413 and 414: Author Index 0 Duskova, J.: P06.012
Page 415 and 416: Author Index Franke, A.: P09.056 Fr
Page 417 and 418: Author Index Grasso, R.: P02.025 Gr
Page 419 and 420: Author Index Holder-Espinasse, M.:
Page 421 and 422: Author Index Jurkiewicz, E.: C14.5
Page 423 and 424: Author Index Kooper, A. J. A.: P05.
Page 425 and 426: Author Index Li, K. J.: P11.086 Li,
Page 427 and 428: Author Index Martinet, D.: P03.095
Page 429 and 430:
Author Index Moorman, A. F. M.: P16
Page 431 and 432:
Author Index P10.57, P10.82 Oguzkan
Page 433 and 434:
Author Index P09.054, P09.085, P09.
Page 435 and 436:
Author Index P16.01 Renieri, A.: P0
Page 437 and 438:
Author Index Santorelli, F.: P08.55
Page 439 and 440:
Author Index Sinke, R. J.: P02.020
Page 441 and 442:
Author Index Taheri, M.: P04.33, P0
Page 443 and 444:
Author Index Valentino, P.: P02.064
Page 445 and 446:
Author Index Wiemer-Kruel, A.: P14.
Page 447 and 448:
Keyword Index 1 10q22 deletions: P0
Page 449 and 450:
Keyword Index autosomal dominant re
Page 451 and 452:
Keyword Index CLA: P06.073 CLCN1 ge
Page 453 and 454:
Keyword Index DMD: P16.40, P16.41,
Page 455 and 456:
Keyword Index gene networks: S12.2
Page 457 and 458:
Keyword Index hydrocephaly: P05.11
Page 459 and 460:
Keyword Index malignant hyperthermi
Page 461 and 462:
Keyword Index NAT2: P12.118 natridi
Page 463 and 464:
Keyword Index Polymalformations: P0
Page 465 and 466:
Keyword Index Sardinia: C09.6 Sardi
Page 467 and 468:
Keyword Index TNFalpha: P08.61, P09
Page 469:
ican
show all

2009 Vienna - European Society of Human Genetics

Create successful ePaper yourself

Delete template?

Save as template?