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DMP07 Neonatal presentations in Angelman syndrome
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Abstracts: Poster Presentations, the Seventh European Paediatric Neurology Society (EPNS) Congress
DMP05 Genetic analysis of a large family with idiopathic congenital motor nystagmus reveals a novel missense mutation Y. Kaplan1 *, I˙. Vargel2 , T. Kansu3 , B. Akin4 , E. Rohmann5 , 7 ¨ celik S. Kamaci6 , E. Uz4 , T. Oz ¸ , B. Wollnik5 , N. Akarsu4 . 1 Department of Molecular Biology and Genetics, Bilkent University, 2 Department of Orthodontics, Hacettepe University, Faculty of Dentistry, Ankara, Turkey, 3 Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany, 4 Gene Mapping Laboratory, Pediatric Hematology Unit, 5 Department of Neurology, Neuro-Ophthalmology Unit, 6 Department of Plastic and Reconstructive Surgery, Hacettepe University Medical Faculty, Ankara, 7 Department of Neurology, Gaziosmanpasa University Medical Faculty, Tokat, Turkey Background: X-linked idiopathic congenital motor nystagmus (NYS1) is a common form of nystagmus. Two distinct loci, one on Xq26-q27 and the other on Xp11.4 were previously reported for NYS1. Recently, FRMD7 (FERM domain-containing 7) mutations were identified in the Xq26 linked families. Aim: To identify underlying genetic defect of a six generation Turkish family with a total of 162 individuals, 28 of whom are affected by idiopathic congenital motor nystagmus. Methods: A total of 17 patients underwent neuro-ophthalmological examination. Both Xp11 and Xq26 loci were first tested by linkage analysis. The 12 exons and intro-exon junctions of the FRMD7 gene were further screened by direct sequencing. X chromosome inactivation analysis was performed by enzymatic predigestion of DNA. Results: 27% penetrance was observed in female obligate carriers. Genetic linkage analysis confirmed the Xq26 locus and further mutation screen identified a novel missense c.686C>G mutation in the exon 8 of the FRMD7 gene which causes a substitution of a conserved arginine at amino acid position 229 by glycine (p.R229G) was observed. No similar change was documented in 240 control chromosomes. Conclusion: Families with different ethnical origin linked to Xq26 suggests that this locus is the most common cause of NYS1 phenotype and a novel p. R229G mutation in the FRMD7 gene causes x-linked nystagmus phenotype. DMP06 Have trisomy 21 babies more proteins in their cells’ nuclei than those of controls? Z. Hamurcu1 *, H. Demirtas2 , S. Kumandas3 , T. Patiroglu3 . 1 College of Physical Education and Sports, 2 Medical Biology Dept, Faculty of Medicine3 Pediatrics Dept, Faculty of Medicine, Erciyes University, Kayseri, Turkey Down syndrome (DS) or trisomy 21 (Ts21) is the most common genetic cause of mental retardation, immunodeficiency, congenital heart disease and some other inter-individually variable defects with an incidence of 1 in 750 live birth. The DS phenotype is assumed to occur primarily by the expression/over-expression of some genes encoded by the extra-chromosome 21. It has recently been shown that babies with Ts21 have more AgNOR area (more NORs proteins) and more RNA content in their peripheral blood mononuclear cells (PBMC) than those of controls. The aim of this study is to test whether or not the nuclear proteins content of trisomy 21 infants is higher than that of the controls. For this purpose, flow cytometric measurement of the stained PBMC nuclei was used. Nuclei from PBMC was isolated and stained with propidium iodide and fluorescein isothiocyanate (PI/FITC) for DNA and proteins measurement respectively. Mean nuclear protein content of Ts21’s (N = 28, mean age = 3.68±3.03 years old) PBMC was found statistically higher than that of the controls (N = 22, mean age = 3.81±2.24 years old), (P = 0.007, 2-tailed independent sample t-test). This means that average nuclear protein content of PBMC from Ts21 infants is higher than that of the controls. Furthermore, there is a moderate
negative correlation between the ages of DS patients and the protein content in the nuclei of their PBMCs (P = 0.005, r = −0.52). This correlation is not found with controls (P = 0, 588, r = 0.12). We have concluded that protein traffic between nucleus and cytoplasm in PBMCs from DS patients is different from that of the controls. DMP07 Neonatal presentations in Angelman syndrome N.J.V. Cordeiro2 *, A. Ahmed1 , R. Davidson1 , R. McWilliam2 . 1 Duncan Guthrie Department of Medical Genetics, 2 Fraser of Allander Neurosciences Unit, Royal Hospital for Sick Children, Yorkhill, Glasgow, UK Early diagnosis of Angelman syndrome eludes clinicians and EEG can be of use. We contrast two children in whom difficulties were present from the neonatal period, and emphasise the value of genetics liaison in making an early diagnosis in the absence of characteristic EEG features. 1. Irritability, tone abnormalities and feeding difficulties in the neonatal period suggested neonatal encephalopathy. Abnormal tone and feeding difficulties continued in infancy. Development of a myoclonic epilepsy at 4 years preceded formal diagnosis. A de-novo deletion was detected. 2. Low muscle tone and accompanying feeding difficulties requiring parenteral nutrition were noted in the neonatal period and suggested neonatal encephalopathy. A picture of neonatal hepatitis resolved spontaneously and investigation was unremarkable. In infancy evolving microcephaly, motor delay and strabismus were noted. A genetics review suggested the diagnosis at the age of 18 months, in the context of a new onset seizure disorder. Uniparental disomy was detected. Discussion: EEG is a tool and interictal manifestations of Angelman syndrome should not be given undue weight to the detriment of other features. Genetics liaison allows appreciation of an early evolving gestalt, aided by knowledge of the rapidly evolving genetics of epilepsy. Neonatal features of Angelman syndrome deserve further study. DMP08 Interstitial deletion of a proximal 3p: a clinically recognisable syndrome C. Lalli, C. Galasso, A. Lo Castro, A.M. Nardone, A. Di Paolo, P. Curatolo *. Pediatric Neurology Unit, Neuroscience Dept., Tor Vergata University, Rome, Italy Interstitial deletion of the proximal short arm of chromosome 3 is rare. In literature only 13 patients with this chromosomal rearrangement at different breakpoints have been reported, and eight of these deletions included chromosome band 3p12. On the basis of the first reports, Neri et al. suggested a “proximal 3p deletion phenotype” characterized by typical facies, limitation of joint mobility, deformity of hands and feet, delayed psychomotor development. In the present study, we report a new case of a de novo 46, XX.ish del(3)(p12.3p12.1) with distinctive face, cleft palate, mild rhizomelia, tracheomalacy, hydronephrosis and ureteric dilatation of right kidney, hypotonia, and mental retardation. In the 3p12 band, only a small number of known genes, including ROBO1 and ROBO2, are present in the deleted region.ROBO genes play an important role in axon guidance across the midline during central nervous system development. Moreover, the ROBO1 gene encodes for a receptor that is a member of the neural cell adhesion molecule family of receptors, and it has been reported in learning disabilities, especially in dyslexia. Interestingly, developmental difficulties involving notable delay in language acquisition are often observed in patients with deletion of the 3p12 band.
Abstracts: Poster Presentations, the Seventh European Paediatric Neurology Society (EPNS) Congress
DMP05 Genetic analysis of a large family with idiopathic congenital motor nystagmus reveals a novel missense mutation Y. Kaplan1 *, I˙. Vargel2 , T. Kansu3 , B. Akin4 , E. Rohmann5 , 7 ¨ celik S. Kamaci6 , E. Uz4 , T. Oz ¸ , B. Wollnik5 , N. Akarsu4 . 1 Department of Molecular Biology and Genetics, Bilkent University, 2 Department of Orthodontics, Hacettepe University, Faculty of Dentistry, Ankara, Turkey, 3 Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany, 4 Gene Mapping Laboratory, Pediatric Hematology Unit, 5 Department of Neurology, Neuro-Ophthalmology Unit, 6 Department of Plastic and Reconstructive Surgery, Hacettepe University Medical Faculty, Ankara, 7 Department of Neurology, Gaziosmanpasa University Medical Faculty, Tokat, Turkey Background: X-linked idiopathic congenital motor nystagmus (NYS1) is a common form of nystagmus. Two distinct loci, one on Xq26-q27 and the other on Xp11.4 were previously reported for NYS1. Recently, FRMD7 (FERM domain-containing 7) mutations were identified in the Xq26 linked families. Aim: To identify underlying genetic defect of a six generation Turkish family with a total of 162 individuals, 28 of whom are affected by idiopathic congenital motor nystagmus. Methods: A total of 17 patients underwent neuro-ophthalmological examination. Both Xp11 and Xq26 loci were first tested by linkage analysis. The 12 exons and intro-exon junctions of the FRMD7 gene were further screened by direct sequencing. X chromosome inactivation analysis was performed by enzymatic predigestion of DNA. Results: 27% penetrance was observed in female obligate carriers. Genetic linkage analysis confirmed the Xq26 locus and further mutation screen identified a novel missense c.686C>G mutation in the exon 8 of the FRMD7 gene which causes a substitution of a conserved arginine at amino acid position 229 by glycine (p.R229G) was observed. No similar change was documented in 240 control chromosomes. Conclusion: Families with different ethnical origin linked to Xq26 suggests that this locus is the most common cause of NYS1 phenotype and a novel p. R229G mutation in the FRMD7 gene causes x-linked nystagmus phenotype. DMP06 Have trisomy 21 babies more proteins in their cells’ nuclei than those of controls? Z. Hamurcu1 *, H. Demirtas2 , S. Kumandas3 , T. Patiroglu3 . 1 College of Physical Education and Sports, 2 Medical Biology Dept, Faculty of Medicine3 Pediatrics Dept, Faculty of Medicine, Erciyes University, Kayseri, Turkey Down syndrome (DS) or trisomy 21 (Ts21) is the most common genetic cause of mental retardation, immunodeficiency, congenital heart disease and some other inter-individually variable defects with an incidence of 1 in 750 live birth. The DS phenotype is assumed to occur primarily by the expression/over-expression of some genes encoded by the extra-chromosome 21. It has recently been shown that babies with Ts21 have more AgNOR area (more NORs proteins) and more RNA content in their peripheral blood mononuclear cells (PBMC) than those of controls. The aim of this study is to test whether or not the nuclear proteins content of trisomy 21 infants is higher than that of the controls. For this purpose, flow cytometric measurement of the stained PBMC nuclei was used. Nuclei from PBMC was isolated and stained with propidium iodide and fluorescein isothiocyanate (PI/FITC) for DNA and proteins measurement respectively. Mean nuclear protein content of Ts21’s (N = 28, mean age = 3.68±3.03 years old) PBMC was found statistically higher than that of the controls (N = 22, mean age = 3.81±2.24 years old), (P = 0.007, 2-tailed independent sample t-test). This means that average nuclear protein content of PBMC from Ts21 infants is higher than that of the controls. Furthermore, there is a moderate
negative correlation between the ages of DS patients and the protein content in the nuclei of their PBMCs (P = 0.005, r = −0.52). This correlation is not found with controls (P = 0, 588, r = 0.12). We have concluded that protein traffic between nucleus and cytoplasm in PBMCs from DS patients is different from that of the controls. DMP07 Neonatal presentations in Angelman syndrome N.J.V. Cordeiro2 *, A. Ahmed1 , R. Davidson1 , R. McWilliam2 . 1 Duncan Guthrie Department of Medical Genetics, 2 Fraser of Allander Neurosciences Unit, Royal Hospital for Sick Children, Yorkhill, Glasgow, UK Early diagnosis of Angelman syndrome eludes clinicians and EEG can be of use. We contrast two children in whom difficulties were present from the neonatal period, and emphasise the value of genetics liaison in making an early diagnosis in the absence of characteristic EEG features. 1. Irritability, tone abnormalities and feeding difficulties in the neonatal period suggested neonatal encephalopathy. Abnormal tone and feeding difficulties continued in infancy. Development of a myoclonic epilepsy at 4 years preceded formal diagnosis. A de-novo deletion was detected. 2. Low muscle tone and accompanying feeding difficulties requiring parenteral nutrition were noted in the neonatal period and suggested neonatal encephalopathy. A picture of neonatal hepatitis resolved spontaneously and investigation was unremarkable. In infancy evolving microcephaly, motor delay and strabismus were noted. A genetics review suggested the diagnosis at the age of 18 months, in the context of a new onset seizure disorder. Uniparental disomy was detected. Discussion: EEG is a tool and interictal manifestations of Angelman syndrome should not be given undue weight to the detriment of other features. Genetics liaison allows appreciation of an early evolving gestalt, aided by knowledge of the rapidly evolving genetics of epilepsy. Neonatal features of Angelman syndrome deserve further study. DMP08 Interstitial deletion of a proximal 3p: a clinically recognisable syndrome C. Lalli, C. Galasso, A. Lo Castro, A.M. Nardone, A. Di Paolo, P. Curatolo *. Pediatric Neurology Unit, Neuroscience Dept., Tor Vergata University, Rome, Italy Interstitial deletion of the proximal short arm of chromosome 3 is rare. In literature only 13 patients with this chromosomal rearrangement at different breakpoints have been reported, and eight of these deletions included chromosome band 3p12. On the basis of the first reports, Neri et al. suggested a “proximal 3p deletion phenotype” characterized by typical facies, limitation of joint mobility, deformity of hands and feet, delayed psychomotor development. In the present study, we report a new case of a de novo 46, XX.ish del(3)(p12.3p12.1) with distinctive face, cleft palate, mild rhizomelia, tracheomalacy, hydronephrosis and ureteric dilatation of right kidney, hypotonia, and mental retardation. In the 3p12 band, only a small number of known genes, including ROBO1 and ROBO2, are present in the deleted region.ROBO genes play an important role in axon guidance across the midline during central nervous system development. Moreover, the ROBO1 gene encodes for a receptor that is a member of the neural cell adhesion molecule family of receptors, and it has been reported in learning disabilities, especially in dyslexia. Interestingly, developmental difficulties involving notable delay in language acquisition are often observed in patients with deletion of the 3p12 band.