2009 Vienna - European Society of Human Genetics

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Clinical genetics and Dysmorphology ed with the recessive form of this condition: they have clubbed fingers, painful periostitis, excessive sweating on hands and feet, thickening of the limbs particularily knees with arthralgia of large and small joints, and paroxysomally occurring bone pains. All these symptoms started after the first few years of life. Radiologically, cortical thickening and sclerosis of the tubular bones with expansion of the diaphyses, and Wormian bones of the skull were shown. The bone symptoms grossly faded away - however pain attacks and hyperhidrosis still persist. Molecular analysis demonstrated the presence of frameshift mutations of both HPGD alleles: c.120delA (paternal) and c.175_176 del- CT (maternal). The heterozygous parents are healthy. Investigation of the presumably increased PGE2-excretion is under way. Conclusion. Given the causality between the painful clinical symptoms and disturbance of the prostaglandine metabolism, antagonist drugs like indomethacin may alleviate clinical symptoms, using PGE2-excretion as a useful monitoring of this therapy. P02.158 Blomstrand dysplasia - evidence of founder effect in a small northeast Brazilian region M. T. Sakata 1 , G. Bertrand 2 , C. Silve 2 , C. A. Moreno 1 , D. P. Cavalcanti 1 ; 1 Programa de Genética Perinatal, Dept Genética Médica, UNICAMP, Campinas, Brazil, 2 Hôpital St Vincent de Paul INSERM U561, Paris, France. Blomstrand Dysplasia (BD), a lethal osteochondrodysplasia (OCD), is characterized by osteosclerosis, carpo-tarsal advanced maturation, narrow thorax with clavicles and ribs thickening, and short limbs displaying a dumb-bell appearance of the tubular bones. Other features are hydrops, macroglossia, and atelia. Recessive inheritance was recently confirmed by the description of homozygous mutations in the PTHR1 gene. In this report we present a study of two new families coming from three near small cities of the Brazilian northeast region. Consanguinity was not referred by the parents of the first studied family and the proband’s clinical-radiological natal examination revealed a typical phenotype of BD. In the other studied family, the parents are consanguineous and the proband’s radiological-clinical evaluation confirmed the BD diagnosis. In both probands an identical single homozygous point mutation at position -2 of the 5’ consensus acceptor site at the exon 9 (c.639 -2 A>G) was identified after PCR amplification of all coding exons and intron-exon junctions of the PTHR1 gene. The point mutation was present at the heterozygous state in the proband 1’s parents. This mutation is expected to result in a loss of function of the PTHR1. On the fifteen BD cases previously reported, one was exactly from the same region referred for the families here reported. In conclusion, considering that three families have segregated this rare condition come from the same region and the fact that in two of the probands were found the same mutation, we suggest a founder effect in BD at the Brazilian northeast region. P02.159 molecular diagnosis in Pycnodysostosis P. Rendeiro, R. Cerqueira, L. Lameiras, H. Gabriel, L. Dias, A. Palmeiro, M. Tavares; CGC Genetics (www.cgcgenetics.com), Porto, Portugal. Introduction: Pycnodysostosis is a rare autosomal recessive trait, characterized by osteosclerosis, short stature, acro-osteolysis of the distal phalanges, bone fragility, clavicular dysplasia, and skull deformities with delayed suture closure. The responsible gene, cathepsin K (CTSK), is a lysosomal cysteine proteinase critical for bone remodeling and reabsorption. CTSK spans approximately 12 kb in 1q21 and contains 8 exons. Its 987bp open reading frame encodes a polypeptide of 329 amino acids. CGC Genetics is a reference laboratory for diagnosing this disease. We report here our experience for the identification of new Pycnodysostosis cases. Method: During 2004-2008, we received 9 samples for CTSK gene analysis. Our approach is the sequence analysis of the complete coding region of this gene including adjacent intron/exon boundaries. At this moment we designed a microarray based assay (patent pending), to be used as a first evaluation that detects 15 mutations and includes those referred in the present work. Results: In 5 patients we found 1 homozygous disease causing mutation plus 2 new mutations (1 nonsense and 1 frameshift). One patient with 1 causative mutation and 1 new amino acid change, and 1 patient with 1 new homozygous amino acid change. In the remaining 2 patients, no mutation was identified. The newly detected amino acid change, in two cases, is predicted to be damaging. Conclusion: These results, with four new mutations identified in unrelated families, emphasize the molecular heterogeneity of the defects in CTSK gene in Picnodysiostosis and the importance of genotyping for diagnosis and genetic counseling. P02.160 type 3 Rhizomelic chondrodysplasia punctata in a patient: A case report of a very rare disorder E. Karaca, S. Basaran Yılmaz, E. Yosunkaya, G. S. Güven, M. Seven, A. Yüksel; Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Genetics, Istanbul, Turkey. Rhizomelic chondrodysplasia punctata (RCDP) is an autosomal recessive disorder, characterized by severe limb shortening, punctate calcification of cartilage, flexion contractures, vertebral clefts, cataracts, characteristic facial appearance, severe growth deficiency and mental retardation. Three genotypes have been identified. Type 1 is associated with a defect in the PEX7 gene, which codes for the receptor of peroxisome targeting sequence 2. In Type 2, there is an isolated deficiency of DHAP acyltransferase, and in Type 3, a defect of alkyl-DHAP synthase. Plasmalogen levels are reduced in type 2 and 3 patients, while phytanic acid levels and the processing of 3-ketothiolase are normal. Here, we present a 3 5/12 years old patient, born to first cousin parents. He was first referred to our clinic, when he was 5 months old, because of growth delay, rhizomelic shortening of limbs, bilateral cataracts, and facial dysmorphism. His physical examination revealed that he had severe short stature, large anterior fontanel, microcephaly, high sloping forehead, micrognathia, bilateral cataracts, low and broad nasal bridge, anteverted nostrils, contractures, osteopenia, irregular vertebral endplates, rhizomelic shortening of all limbs. Skeletal radiologic studies displayed punctate calcifications on a number of cartilages. Biochemical investigations of fibroblasts revealed deficient alkyl-DHAP synthase. In conclusion, based on clinical picture and biochemical enzyme assay the diagnosis of Rhizomelic chondrodysplasia punctata type 3, which is an extremely rare disorder, has been diagnosed in this patient. P02.161 A new classification system for segmentation defects of the vertebrae, and pilot validation study P. D. Turnpenny 1 , A. Offiah 2 , P. F. Giampietro 3 , B. Alman 4 , A. S. Cornier 5 , K. Kusumi 6 , S. Dunwoodie 7 , A. Ward 8 , O. Pourquié 9 , Intnl Consortium for Vertebral Anomalies & Scoliosis (ICVAS); 1 Peninsula Clinical Genetic Service, Exeter, United Kingdom, 2 Great Ormond Street Hospital, London, United Kingdom, 3 University of Wisconsin, Madison, WI, United States, 4 University of Toronto, Toronto, ON, Canada, 5 La Concepción Hospital, San Germán, Puerto Rico, 6 Arizona State University & UA College of Medicine, Phoenix, AZ, United States, 7 Victor Chang Cardiac Research Institute, Darlinghurst NSW, Australia, 8 Institute of Child Health, London, United Kingdom, 9 Stowers Institute for Medical Research, Kansas City, MO, United States. The study aimed to develop and assess a new classification system for Segmentation Defects of the Vertebrae (SDV), a frequent cause of congenital scoliosis. Existing nomenclature for the wide range of SDV phenotypes is inadequate and confusing, eg ‘Jarcho-Levin syndrome’. A multidisciplinary group of ICVAS met to formulate a clinically useful classification, based primarily on radiology, and transferable to bioinformatic approaches. SDV are identified by number affected, contiguity, and spinal region(s). The size, shape and symmetry of the thoracic cage, and rib number, symmetry and fusion are included, and familiar vertebral morphology terms retained, together with accepted syndrome names. The terms spondylocostal and spondylothoracic dysostosis apply only to phenotypes typified by the monogenic disorders due to mutated DLL3, MESP2, LNFG and HES7 genes. Five IC- VAS members (Group 1) then independently assessed 10 new cases, inter-observer reliability assessed using kappa. Seven independent radiologists (Group 2) then assessed the same cases before and after introduction to the new system. Inter-observer reliability for Group 1 yielded a kappa value of 0.21 (95% confidence intervals (CI) 0.052, 0.366, p=0.0046). For Group 2, before introduction to the new system, 1/70 responses (1.4%) agreed with the Group 1 consensus,12 differ- 0
Clinical genetics and Dysmorphology ent diagnoses were offered, and 38/70 (54.3%) responses were ‘Unknown’. After introduction to the new system 47/70 responses (67.1%; 95% CI 55.5, 77.0) agreed with Group 1 consensus, a 65.7% improvement (95% CI 52.5, 75.6, p
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Volume 17 Supplement 2 May 2009 www
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European Society of Human Genetics
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Table of Contents spoken Presentati
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Plenary Lectures PL2.2 massive para
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Concurrent Symposia s01.1 Genome va
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Concurrent Symposia Monogenic diabe
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Concurrent Symposia invariable in t
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Concurrent Symposia s11.2 clinical,
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Concurrent Symposia s13.2 A novel g
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Concurrent Sessions c01.1 mRNA-seq
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Concurrent Sessions velopmental del
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Concurrent Sessions development of
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Concurrent Sessions c04.6 Duplicati
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Concurrent Sessions genes to be rec
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Concurrent Sessions c07.5 Prenatal
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Concurrent Sessions with familial h
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Concurrent Sessions University of W
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Concurrent Sessions with this, we f
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Concurrent Sessions had immotile ci
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Concurrent Sessions abnormal glycos
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Concurrent Sessions showers’ and
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Page 47 and 48: Genetic counseling Genetics educati
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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
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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
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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
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Cytogenetics P03.183 An atypical 7q
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Cytogenetics spermia, 11 oligosperm
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Reproductive genetics and social fa
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Reproductive genetics mosomal chang
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Reproductive genetics two cohorts w
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Reproductive genetics the 147 SC ch
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Prenatal and perinatal genetics P05
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Prenatal and perinatal genetics and
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Prenatal and perinatal genetics fro
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Prenatal and perinatal genetics dev
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Prenatal and perinatal genetics in
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Prenatal and perinatal genetics obj
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Prenatal and perinatal genetics P05
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Cancer genetics P06.005 tiling reso
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Cancer genetics tient group in whic
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Cancer genetics chronic inflammatio
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Cancer genetics licular thyroid can
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Cancer genetics also studied. In 31
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Cancer genetics tile polyposis. We
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Cancer genetics Upon recombinant ex
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Cancer genetics variant allele was
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Cancer genetics from patients with
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Cancer genetics tion (PAX5 and GATA
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Cancer genetics scribed underexpres
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Cancer genetics of the ZIC gene fam
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Cancer genetics Materials and metho
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Cancer genetics the past and it is
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Cancer genetics P06.130 spectrum an
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Cancer genetics P06.139 the role of
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Cancer genetics and MSH2 germline m
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Cancer genetics P06.155 New roles f
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Cancer genetics screening was perfo
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Cancer genetics val (DFI) than pati
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Cancer genetics is hTERC gene ampli
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Cancer genetics on chromosome regio
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Cancer genetics preferentially dupl
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Cancer cytogenetics mutations in co
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Cancer cytogenetics P07.08 molecula
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Statistical genetics, includes Mapp
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Complex traits and polygenic disord
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Evolutionary and population genetic
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Genomics, Genomic technology and Ep
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Molecular basis of Mendelian disord
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Metabolic disorders P12.167 Pattern
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Metabolic disorders PKU. BH4 challe
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Metabolic disorders catepe Universi
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Metabolic disorders respectively. G
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Metabolic disorders enzymaticaly co
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Metabolic disorders Normal Affected
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Therapy for genetic disorders in th
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Therapy for genetic disorders P14.0
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Therapy for genetic disorders of me
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Laboratory and quality management P
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Laboratory and quality management T
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Molecular and biochemical basis of
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Genetic analysis, linkage ans assoc
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Author Index Allanson, J.: P02.140
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Author Index 0 Barbacioru, C.: C01.
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Author Index 0 Bonneau, D.: C16.2,
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Author Index 0 Chakravarti, A.: C13
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Author Index 0 Dan, D.: P01.39, P14
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Author Index 0 Duskova, J.: P06.012
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Author Index Franke, A.: P09.056 Fr
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Author Index Grasso, R.: P02.025 Gr
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Author Index Holder-Espinasse, M.:
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Author Index Jurkiewicz, E.: C14.5
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Author Index Kooper, A. J. A.: P05.
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Author Index Li, K. J.: P11.086 Li,
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Author Index Martinet, D.: P03.095
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Author Index Moorman, A. F. M.: P16
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Author Index P10.57, P10.82 Oguzkan
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Author Index P09.054, P09.085, P09.
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Author Index P16.01 Renieri, A.: P0
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Author Index Santorelli, F.: P08.55
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Author Index Sinke, R. J.: P02.020
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Author Index Taheri, M.: P04.33, P0
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Author Index Valentino, P.: P02.064
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Author Index Wiemer-Kruel, A.: P14.
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Keyword Index 1 10q22 deletions: P0
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Keyword Index autosomal dominant re
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Keyword Index CLA: P06.073 CLCN1 ge
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Keyword Index DMD: P16.40, P16.41,
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Keyword Index gene networks: S12.2
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Keyword Index hydrocephaly: P05.11
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Keyword Index malignant hyperthermi
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Keyword Index NAT2: P12.118 natridi
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Keyword Index Polymalformations: P0
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Keyword Index Sardinia: C09.6 Sardi
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Keyword Index TNFalpha: P08.61, P09
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2009 Vienna - European Society of Human Genetics

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