European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Recommendations

Info

Molecular and biochemical basis of disease confirmed by southern blot analysis. Therefore, a total of 207 and 212 X-chromosomes were analyzed for the CGG repeat number in FRAXA and GCC repeats in FRAXE respectively. The most frequent FRAXA allele size was 29 CGG repeats (25.6%). 28 repeat containing alleles were the next frequent (16.9 %) allele. A total of 25 FRAXA allelic variants from 11-45 CGG repeats were observed. The most frequent FRAXE allele size had 15 GCC repeats (24.1%) followed by allele containing 18 repeats (18.3%). A total of 20 FRAXE allelic variants from 4-31 GCC repeats were observed. Our study revealed frequency of FRAXA to be 2.5% and FRAXE to be 0% indicating the absence or rarity of FRAXE mutation in our population. P0738. FRAXA locus investigation of mentally retarded patients Z. Daneberga1,2 , Z. Krumina1 , B. Lace1 , D. Bauze1 , N. Pronina1 , R. Lugovska1 ; 1 2 Medical Genetic Clinic, University Children`s Hospital, Riga, Latvia, Riga Stradins University, Riga, Latvia. Mutations at FRAXA locus on distal Xq may cause mental impairment. Most common mutation at FRAXA locus is expansion of CGG triplet repeats located in the 5‘-untranslated region of the fragile X mental retardation-1 (FMR1) gene. The expanded CGG triplet repeats are hypermethylated and the expression of the FMR1 gene is repressed in patients with fragile X syndrome (FXS), which leads to the absence of FMR1 protein (FMRP) and subsequent mental retardation (MR). Normal alleles vary from 6 to 50 CGG repeats. Intermediate alleles 45 - 55 repeats, premutation alleles 59 - 200 repeats, full mutation greater than approximately 200 repeats (methylated). The group of 292 unrelated patients with MR referred from clinical geneticists was screened by PCR for a normal allele. For 179 chromosomes CGG repeats number was detected by Applied Biosystems protocol on ABI Prism 310. The prevalence of 29, 30 and 31 CGG repeats were found. Five affected patients were detected (1.71%). The final diagnosis of FXS confirmed by Southern blotting. In four FXS families we found 4 females permutation carriers, 3 females with full mutation, 3 affected males with full mutation, 1 affected mosaic male. All permutated and mutated alleles in FXS families were associated with single nucleotide polymorphism (SNP) ATL1 allele G. 105 chromosomes of patients with normal CGG repeats number were analyzed for ATL1 SNP. For 62% of analyzed chromosomes ATL1 allele A was found. The estimation of STR-based haplotype structure for further investigation of Latvian FXS patients and their families are in progress. P0739. GAA repeat expansion-associated DNA methylation changes in Friedreich ataxia S. Al-Mahdawi, O. Ismail, D. Varshney, S. Lymperi, R. Mouro Pinto, M. A. Pook; Brunel University, Uxbridge, United Kingdom. Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder that is primarily caused by a GAA repeat expansion mutation within intron 1 of the FXN gene, leading to a decreased level of frataxin protein expression. The mechanism by which this mutation acts is currently unknown, but two models have been put forward. Firstly, it has been suggested that the GAA repeat expansion may adopt an abnormal triplex structure that interferes with FXN gene transcription. Secondly, there is evidence that the GAA repeat expansion is associated with epigenetic changes, such as DNA methylation and modification of histones, producing a heterochromatin-mediated gene silencing effect. In support of this second hypothesis, we have recently obtained data that shows increased DNA methylation of specific CpG sites immediately upstream of the expanded GAA repeat sequence in FRDA patient autopsied brain tissue, compared with non-GAA repeat expansion containing brain tissue. In contrast, no such changes were identified in the FXN promoter region. We have also identified similar DNA methylation increases in brain and heart tissues from our recently established GAA repeat expansion-containing FXN YAC transgenic mouse model, compared with similar non-GAA repeat expansion FXN YAC transgenic mice. These studies will be detailed, together with our more recent investigations to identify potential GAA repeat expansion-associated changes in methylation and acetylation of histones at the FXN locus. Such epigenetic studies to identify the potential GAA repeat expansion mechanism of action will provide valuable information for novel FRDA therapies. P0740. Investigation for point mutations on different parts of Mitochondrial DNA, relating to adjunct of pathogenesis of FRDA, on 20 Iranian patients with Friedreich‘s ataxia S. EtemadAhari 1 , S. Kasraie 1 , M. Houshmand 1 , M. Moin 2 , M. Shafa Shariat Panahi 1 ; 1 Department of Medical genetics, National Research Center of Genetic Engineering and Biotechnology(NIGEB), Tehran, Islamic Republic of Iran, 2 Immunology, Asthma & Allergy Research Institute, Tehran, Iran., Tehran, Islamic Republic of Iran. Friedreich’s ataxia (FA,FRDA) is the most common inherited ataxia. Clinically, FRDA is characterized by multiple symptoms including progressive gait and limb ataxia, dysarthria, diabetes mellitus, and hypertrophic cardiomyopathy. The gene defective in FRDA, encodes a mitochondrial protein known as frataxin. A triplet repeat expansion within intron 1 of the FRDA gene results in a marked decrease in frataxin expression.There is much evidence to suggest that FRDA results from mitochondrial iron accumulation leading to cellular damage and death by the production of toxic free radicals by Fenton chemistry. Due to the important role of the mitochondria and considering the clinical symptoms of FRDA, failure in ATP production and presence of free radicals in mitochondria of patients with FRDA we are analyzing different parts of mtDNA; MT-ATP8 , MT-ATP6, and highly mutative genes like; MT-LTI , MT-NDI, MT-COII, MT-TK, in 20 Iranian FRDA patients to find any probable point mutation by PCR method and automated DNA sequence that can be involved as an adjunct in the pathogenesis of FRDA P0741. Hypomethylation is restricted to the D4Z4 repeat array in phenotypic FSHD J. C. de Greef 1 , M. Wohlgemuth 2 , O. A. Chan 1 , K. B. Hansson 3 , D. Smeets 4 , R. R. Frants 1 , C. M. Weemaes 5 , G. W. Padberg 2 , S. M. van der Maarel 1 ; 1 Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands, 2 Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, 3 Clinical Cytogenetics Laboratory, LDGA, Leiden University Medical Center, Leiden, The Netherlands, 4 Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, 5 Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant myopathy affecting predominantly the muscles of the face, shoulder and upper arm. Most FSHD patients show a contraction of the D4Z4 repeat array in the subtelomere of chromosome 4q. This contraction is associated with significant allele-specific hypomethylation of the repeat, suggestive for a chromatin restructuring at 4qter in FSHD. Hypomethylation of D4Z4 is also observed in phenotypic FSHD patients without D4Z4 contraction and in patients suffering from the immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome, an unrelated disorder that does not present with muscular dystrophy and is in part caused by mutations in the DNMT3B gene. In order to identify the gene defect in phenotypic FSHD and to unravel the pathogenic epigenetic pathway in FSHD, we have aimed to identify the differences and commonalities in phenotypic FSHD and the ICF syndrome by (1) investigation of DNA methylation of non-D4Z4 repeat arrays, (2) analysis of mitogen-stimulated lymphocytes to detect pericentromeric abnormalities involving chromosomes 1, 9 and 16, (3) determination of IgA, IgG and IgM levels and (4) mutational analysis of candidate genes to identify a second disease locus involved in the pathogenesis of phenotypic FSHD. Our results do not show epigenetic or phenotypic commonalities between phenotypic FSHD and ICF other than the earlier observed D4Z4 hypomethylation, suggesting that phenotypic FSHD is not caused by a defect in the same molecular pathway as ICF. We neither could identify any mutations in the candidate genes tested for. P0742. Comprehensive mutation analysis in a clinically well defined cohort of patients with exudative vitreoretinopathy. L. H. Hoefsloot 1 , C. E. van Nouhuys 2 , N. Boonstra 3 , J. Schuil 3 , I. J. de Wijs 1 , K. P. van der Donk 1 , K. Nikopoulos 1 , A. Mukhopadhyay 1 , H. Scheffer 1 , M. A. D. Tilanus 4 , F. P. M. Cremers 1 ; 1 Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 2 Department of Ophthalmology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands, 3 Bartimeus Institute for the Visually Impaired, Zeist, The Netherlands, 4 Department of Ophthalmology, Radboud 1
Molecular and biochemical basis of disease University Nijmegen Medical Centre, Nijmegen, The Netherlands. Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by vitroretinal pathology. Retinal exudates, retinal neovascularisation, retinal folds and retinal detachment as well as vitreous haemorrhage have been described to occur in the first decade of life. The disease is slowly progressive, with in the terminal stages of severely affected eyes a chronic retinal detachment, leading to total blindness. To date, 3 genes and 1 locus have been described. FZD4 mutations were found in patients with autosomal dominant EVR. Xlinked EVR is caused by mutations in NDP, and LRP5 mutations can be inherited both automal dominant as well as autosomal recessive. The EVR3 (605750) locus maps to 11p12-p13. In a series of 30 sporadic patients and dominant families, we analysed the involvement of the NDP, FZD4 and LRP5 genes by sequence analysis. We found in one patient a mutation in the NDP gene. Mutations in the FZD4 gene were found in approximately 30% of the patients and families, (9/30), with the c.957G>A (p.Trp319X) mutation as the most frequent mutation (5/30). The analysis of LRP5 revealed a mutation in one family, and an alteration of unknown pathogenicity in another. Careful clinical evaluation of the patients will lead to determination of a possible relationship between phenotype and genotype in this cohort. Furthermore, families without a mutation in one of the known genes, will help to identify new loci for FEVR. P0743. Molecular Identification of Mutations in G6PD Gene in Patients in Kerman and Yazd Provinces of Iran. M. Noori-Daloii; Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences Tehran,, Tehran, Islamic Republic of Iran. Glucose- 6-phosphate dehydrogenase (G6PD) is a housekeeping enzyme and its gene is located on the Xq28 region of X chromosome. G6PD deficiency is one of the most common inherited disorders of mankind affecting more than 400 million people worldwide. The main clinical manifestations are neonatal jaundice and acute hemolytic. More than 130 mutations and 400 biochemical variants have been reported. Since, the variants including Mediterranean, G6PDA - and Chatham are reported in all over the world, and among them Mediterranean variant is the most common, also in Arabic countries and Persian Gulf, in this study, we investigated Mediterranean, Chatham, Cozenza and A - mutations in the central areas of Iran. The extracted DNA from 119 patients with history of favism was analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for above mutations. The results determined that, from the total 119 samples, 41 samples from state of Kerman (63%) and 35 samples from state of Yazd (64%) hence a total of 63.86% had G6PD Mediterranean and 2 from each states had G6PD Chatham (3.36%). Cosenza and A - mutation were not observed. G6PD Mediterranean was the commonest mutation in Iran and the most of other countries in tropical and subtropical areas. The frequency of Chatham was the second minimum in Central provinces in comparison with others in Iran. The Major ethnic groups in this region are Fars, Arab Turk and minorities of Kurd. For unknown samples other Methods such as SSCP and DNA sequencing are using to determine other mutations. P0744. A new Vohwinkel-like disease is caused by a novel missense mutation in GJB2 M. A. M. Van Steensel1 , E. de Zwart-Storm1 , H. Hamm2 , M. van Geel1 ; 1 2 University of Maastricht, Maastricht, The Netherlands, University of Würzburg, Würzburg, Germany. Gap junctions are intercellular channels that mediate rapid intercellular communication. They consist of connexins, small transmembrane proteins that belong to a large family found throughout the animal kingdom. In the skin, several connexins are expressed and are involved in the regulation of epidermal growth and differentiation. The gap junction gene GJB2, that codes for the protein connexin26, is highly expressed in the epidermis and is associated with a wide variety of diseases, showing a strong genotype-phenotype correlation. Despite extensive research in the past few years, this phenomenon is poorly understood. The identification of novel diseases caused by mutations in GJB2 may help to shed light on its strong genotype-phenotype correlation and help elucidate the function of different parts of the protein. Here, we report on a novel GJB2 mutation that causes a syndrome of focal palmoplantar keratoderma with sensorineural deafness, a phenotype that is reminiscent of Vohwinkel’s disease. Using fluorescent fusion proteins, we show that the mutation causes a transport defect similar to that found for the Vohwinkel syndrome mutation D66H. P0745. Genetic polymorphism of glutathione-S-transferase T1 and M1 in the newborns with neonatal syndromes in Ukrainian population N. Gorovenko, Z. Rossokha, S. Podolskaya; National Medical Academy of Post-Graduate Education, Kyiv, Ukraine. The more recent discovery suggested the physiological role glutathione-S-transferases (GSTs) in protecting against chronic diseases that arise from oxidative tissue damage. The development of the neonatal syndromes are connected with perinatal hypoxia. The functional allele of these genes may protect from hypoxia and the risk of neonatal syndromes. Material and methods: We conducted a case-control study of 117 cases of severe perinatal pathology with neonatal syndromes, such as: perinatal damage of the central nervous system, respiratory distress syndrome, necrotizing enterocolitis, neonatal jaundice and 70 control group (clinical healthy newborns). Genetic polymorphism of GSTT1 and GSTM1 were detected by multiplex polymerase chain reaction (PCR). Differences in these groups were assessed by χ 2 analyses. Results: In our investigation an increased significant frequency of GSTT1“-“ genotypes among neonates with perinatal pathologies (29,91%) compared to newborns in the control group (12,86%), χ 2 =6.17, PG mutation in the gtPBREM region led to hyperbilirubinaemia. In this study, we analyzed a polymorphic variant located at position -3440 C->A of the gtPBREM flanking the PXR binding site which is not common in the general population but highly frequent in Sardinia. To test the functional consequences of the -3440 variant, we quantified the transactivation activity of the variant in epatic cells. We also evaluated if the PXR receptor could bind to the consensus sequence after Rifampicine treatment. These experiments demonstrated that the -3440 variant does not modify PXR’s binding capacity and shows a prominent transactivation activity compared to the wild type sequence. The -3440 variant could balance the reduced activity of UGT1A1 due to presence of the TA7 allele and would explain the asymptomatic phenotype of patients with the (TA)7/(TA)7 genotype. 1
Page 1 and 2:
Volume 15 Supplement 1 June 2007 ww
Page 3 and 4:
Table of Contents Spoken Presentati
Page 5 and 6:
Plenary Lectures Plenary Lectures P
Page 7 and 8:
Plenary Lectures labile iron can be
Page 9 and 10:
Concurrent Symposia S07. Vertebrate
Page 11 and 12:
Concurrent Symposia S17. Towards a
Page 13 and 14:
Concurrent Symposia 11 at E13.5 sim
Page 15 and 16:
Concurrent Symposia 1 phomagenesis.
Page 17 and 18:
cover cryptic mutations in Drosophi
Page 19 and 20:
Concurrent Sessions first excluded
Page 21 and 22:
Concurrent Sessions of 210 ancestry
Page 23 and 24:
Concurrent Sessions C23. Literature
Page 25 and 26:
Concurrent Sessions a boy with a ty
Page 27 and 28:
Concurrent Sessions C40. Mutation o
Page 29 and 30:
Concurrent Sessions C48. CHROMSCAN:
Page 31 and 32:
Concurrent Sessions C57. RNAi-based
Page 33 and 34:
Concurrent Sessions been replicated
Page 35 and 36:
Concurrent Sessions involved in an
Page 37 and 38:
Concurrent Sessions tion considers
Page 39 and 40:
Clinical genetics lateral neurosens
Page 41 and 42:
Clinical genetics apparently sporad
Page 43 and 44:
Clinical genetics itar syndrome, wh
Page 45 and 46:
Clinical genetics diseases, Foundat
Page 47 and 48:
Clinical genetics P0041. The first
Page 49 and 50:
Clinical genetics EFNB1 was found t
Page 51 and 52:
Clinical genetics of the CSB gene.
Page 53 and 54:
Clinical genetics growth retardatio
Page 55 and 56:
Clinical genetics PCR with a modifi
Page 57 and 58:
Clinical genetics pound heterozygou
Page 59 and 60:
Clinical genetics plicated: two cou
Page 61 and 62:
Clinical genetics P0105. APC gene m
Page 63 and 64:
Clinical genetics an indication of
Page 65 and 66:
Clinical genetics great importance
Page 67 and 68:
Clinical genetics P0133. Hidrotic e
Page 69 and 70:
Clinical genetics eight patients as
Page 71 and 72:
Clinical genetics P0152. Kabuki syn
Page 73 and 74:
Clinical genetics P0161. Intrafamil
Page 75 and 76:
Clinical genetics matter and normal
Page 77 and 78:
Clinical genetics type at 550 bands
Page 79 and 80:
Clinical genetics will be confirmed
Page 81 and 82:
Clinical genetics nosed. Accurate r
Page 83 and 84:
Clinical genetics which has not bee
Page 85 and 86:
Clinical genetics P0217. Partial mo
Page 87 and 88:
Clinical genetics fested progeroid
Page 89 and 90:
Clinical genetics A 29 years old ma
Page 91 and 92:
Clinical genetics ing loss (HHL). I
Page 93 and 94:
Clinical genetics dació Son Llatze
Page 95 and 96:
Clinical genetics These preliminary
Page 97 and 98:
Clinical genetics P0272. Williams S
Page 99 and 100:
Cytogenetics Po02. Cytogenetics P02
Page 101 and 102:
Cytogenetics to reports from Saudi
Page 103 and 104:
Cytogenetics P0298. Female-specific
Page 105 and 106:
Cytogenetics P0306. Lipoatrophic pa
Page 107 and 108:
Cytogenetics 22 leading to the form
Page 109 and 110:
Cytogenetics somal sperm and that o
Page 111 and 112:
Cytogenetics University of Belgrade
Page 113 and 114:
Cytogenetics Within the same metaph
Page 115 and 116:
Cytogenetics Less than 10 cases of
Page 117 and 118:
Cytogenetics lar markers taken from
Page 119 and 120:
Cytogenetics Brain Unaffected Schiz
Page 121 and 122:
Cytogenetics ability with no speech
Page 123 and 124:
Cytogenetics P0389. An age based cy
Page 125 and 126:
Cytogenetics P0399. Molecular Chara
Page 127 and 128:
Cytogenetics ing of complex examina
Page 129 and 130:
Cytogenetics letion in 5q33 in all
Page 131 and 132:
Cytogenetics and his son carried th
Page 133 and 134:
Prenatal diagnosis tion about famil
Page 135 and 136:
Prenatal diagnosis P0443. The risk
Page 137 and 138:
Prenatal diagnosis in house PCR pro
Page 139 and 140:
Prenatal diagnosis P0462. Increased
Page 141 and 142:
Prenatal diagnosis P0471. Preimplan
Page 143 and 144:
Prenatal diagnosis agreement with w
Page 145 and 146:
Prenatal diagnosis of Turner Syndro
Page 147 and 148:
Cancer genetics ously defined for d
Page 149 and 150: Cancer genetics Their frequencies w
Page 151 and 152: Cancer genetics tion Clinic-Portugu
Page 153 and 154: Cancer genetics tric carcinogenesis
Page 155 and 156: Cancer genetics P0532. Secondary ch
Page 157 and 158: Cancer genetics P0542. Differential
Page 159 and 160: Cancer genetics gastric cancer risk
Page 161 and 162: Cancer genetics ania, 3 The Institu
Page 163 and 164: Cancer genetics low: 8% (8/98 sampl
Page 165 and 166: Cancer genetics P0578. Somatic mito
Page 167 and 168: Cancer genetics P0587. Differential
Page 169 and 170: Cancer genetics cinoma (ESCC), whic
Page 171 and 172: Cancer genetics method to measure t
Page 173 and 174: Cancer genetics pression (compared
Page 175 and 176: Cancer genetics to available biolog
Page 177 and 178: Molecular and biochemical basis of
Page 199: Molecular and biochemical basis of
Page 235 and 236: Genetic analysis, linkage, and asso
Page 251 and 252:
Genetic analysis, linkage, and asso
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:
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:
Page 287 and 288:
Normal variation, population geneti
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:
Genomics, technology, bioinformatic
Page 311 and 312:
Page 313 and 314:
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:
Genetic counselling, education, gen
Page 329 and 330:
Page 331 and 332:
Page 333 and 334:
Page 335 and 336:
Page 337 and 338:
Page 339 and 340:
Page 341 and 342:
Page 343 and 344:
Page 345 and 346:
Page 347 and 348:
Therapy for genetic disease Po10. T
Page 349 and 350:
Therapy for genetic disease P1405.
Page 351 and 352:
Therapy for genetic disease exon 7
Page 353 and 354:
Author Index 1 Arslan-Krichner, M.:
Page 355 and 356:
Author Index Borkowska, A.: P1089 B
Page 357 and 358:
Author Index Coviello, D.: P0078, P
Page 359 and 360:
Author Index Estivill, X.: P1216, P
Page 361 and 362:
Author Index Graf, S. A.: P0021 Gra
Page 363 and 364:
Author Index 1 Josifiova, D.: PL07
Page 365 and 366:
Author Index Laurier, V.: C03 Lauri
Page 367 and 368:
Author Index Melo, D. G.: P0260, P0
Page 369 and 370:
Author Index Osorio, P.: P0218 Osta
Page 371 and 372:
Author Index Reese, T.: C06 Regal,
Page 373 and 374:
Author Index 1 Shaposhnikov, S.: P0
Page 375 and 376:
Author Index Touitou, I.: P0733 Tou
Page 377 and 378:
Author Index Xiao, C.: P1241 Xie, G
Page 379 and 380:
Keyword Index ARMR: P0907 array CGH
Page 381 and 382:
Keyword Index Consanguineous marria
Page 383 and 384:
Keyword Index 1 Fronto-temporal dem
Page 385 and 386:
Keyword Index IRF5: P1086 IRF6: P07
Page 387 and 388:
Keyword Index NBS1 gene: P0567 NBS-
Page 389 and 390:
Keyword Index P1085 Rep1: P1104 rep
Page 391 and 392:
Keyword Index vision: P0632 Vitamin
Page 393 and 394:
Notes 1
Page 395 and 396:
A natural choice in Fabry Disease P
show all

European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Create successful ePaper yourself

Delete template?

Save as template?