78 Abstracts: Poster Presentations, the Seventh European Paediatric Neurology Society (EPNS) Congress

DMP05 Genetic analysis of a large family with idiopathiccongenital motor nystagmus reveals a novelmissense mutation

Y. Kaplan1 *, I. Vargel2, T. Kansu3, B. Akin4, E. Rohmann5,S. Kamaci6, E. Uz4, T. Ozcelik7, B. Wollnik5, N. Akarsu4.1Department of Molecular Biology and Genetics, Bilkent University,2Department of Orthodontics, Hacettepe University, Facultyof Dentistry, Ankara, Turkey, 3Center for Molecular MedicineCologne (CMMC), University of Cologne, Cologne, Germany, 4GeneMapping Laboratory, Pediatric Hematology Unit, 5Department ofNeurology, Neuro-Ophthalmology Unit, 6Department of Plasticand Reconstructive Surgery, Hacettepe University Medical Faculty,Ankara, 7Department of Neurology, Gaziosmanpasa UniversityMedical Faculty, Tokat, Turkey

Background: X-linked idiopathic congenital motor nystagmus(NYS1) is a common form of nystagmus. Two distinctloci, one on Xq26-q27 and the other on Xp11.4 werepreviously reported for NYS1. Recently, FRMD7 (FERMdomain-containing 7) mutations were identified in the Xq26linked families.Aim: To identify underlying genetic defect of a six generationTurkish family with a total of 162 individuals, 28 of whom areaffected by idiopathic congenital motor nystagmus.Methods: A total of 17 patients underwent neuro-ophthal-mological examination. Both Xp11 and Xq26 loci were firsttested by linkage analysis. The 12 exons and intro-exonjunctions of the FRMD7 gene were further screened bydirect sequencing. X chromosome inactivation analysis wasperformed by enzymatic predigestion of DNA.Results: 27% penetrance was observed in female obligatecarriers. Genetic linkage analysis confirmed the Xq26 locusand further mutation screen identified a novel missensec.686C>G mutation in the exon 8 of the FRMD7 gene whichcauses a substitution of a conserved arginine at amino acidposition 229 by glycine (p.R229G) was observed. No similarchange was documented in 240 control chromosomes.Conclusion: Families with different ethnical origin linked toXq26 suggests that this locus is the most common cause ofNYS1 phenotype and a novel p. R229G mutation in the FRMD7gene 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. Patiroglu3.1College of Physical Education and Sports, 2Medical Biology Dept,Faculty of Medicine3Pediatrics Dept, Faculty of Medicine, ErciyesUniversity, Kayseri, Turkey

Down syndrome (DS) or trisomy 21 (Ts21) is the most com-mon genetic cause of mental retardation, immunodeficiency,congenital heart disease and some other inter-individuallyvariable defects with an incidence of 1 in 750 live birth.The DS phenotype is assumed to occur primarily by theexpression/over-expression of some genes encoded by theextra-chromosome 21. It has recently been shown that babieswith Ts21 have more AgNOR area (more NORs proteins) andmore RNA content in their peripheral blood mononuclearcells (PBMC) than those of controls. The aim of this study is totest whether or not the nuclear proteins content of trisomy21 infants is higher than that of the controls. For this purpose,flow cytometric measurement of the stained PBMC nucleiwas used. Nuclei from PBMC was isolated and stained withpropidium iodide and fluorescein isothiocyanate (PI/FITC) forDNA and proteins measurement respectively. Mean nuclearprotein content of Ts21’s (N=28, mean age =3.68±3.03 yearsold) PBMC was found statistically higher than that of thecontrols (N=22, mean age =3.81±2.24 years old), (P = 0.007,2-tailed independent sample t-test). This means that averagenuclear protein content of PBMC from Ts21 infants is higherthan that of the controls. Furthermore, there is a moderate

negative correlation between the ages of DS patients andthe 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 betweennucleus and cytoplasm in PBMCs from DS patients is differentfrom that of the controls.

DMP07 Neonatal presentations in Angelman syndrome

N.J.V. Cordeiro2 *, A. Ahmed1, R. Davidson1, R. McWilliam2.1Duncan Guthrie Department of Medical Genetics, 2Fraser ofAllander Neurosciences Unit, Royal Hospital for Sick Children,Yorkhill, Glasgow, UK

Early diagnosis of Angelman syndrome eludes clinicians andEEG can be of use. We contrast two children in whomdifficulties were present from the neonatal period, andemphasise the value of genetics liaison in making an earlydiagnosis 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 ininfancy. Development of a myoclonic epilepsy at 4years preceded formal diagnosis. A de-novo deletion wasdetected.

2. Low muscle tone and accompanying feeding difficul-ties requiring parenteral nutrition were noted in theneonatal period and suggested neonatal encephalopathy.A picture of neonatal hepatitis resolved spontaneouslyand investigation was unremarkable. In infancy evolvingmicrocephaly, motor delay and strabismus were noted.A genetics review suggested the diagnosis at the age of18 months, in the context of a new onset seizure disorder.Uniparental disomy was detected.

Discussion: EEG is a tool and interictal manifestations ofAngelman syndrome should not be given undue weightto the detriment of other features. Genetics liaison allowsappreciation of an early evolving gestalt, aided by knowledgeof the rapidly evolving genetics of epilepsy. Neonatal featuresof Angelman syndrome deserve further study.

DMP08 Interstitial deletion of a proximal 3p: a clinicallyrecognisable syndrome

C. Lalli, C. Galasso, A. Lo Castro, A.M. Nardone, A. Di Paolo,P. Curatolo*. Pediatric Neurology Unit, Neuroscience Dept., TorVergata University, Rome, Italy

Interstitial deletion of the proximal short arm of chromosome3 is rare. In literature only 13 patients with this chromosomalrearrangement at different breakpoints have been reported,and eight of these deletions included chromosome band3p12. On the basis of the first reports, Neri et al. suggesteda “proximal 3p deletion phenotype” characterized by typicalfacies, limitation of joint mobility, deformity of hands andfeet, 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, tra-cheomalacy, hydronephrosis and ureteric dilatation of rightkidney, hypotonia, and mental retardation. In the 3p12 band,only a small number of known genes, including ROBO1and ROBO2, are present in the deleted region.ROBO genesplay an important role in axon guidance across the midlineduring central nervous system development. Moreover, theROBO1 gene encodes for a receptor that is a member ofthe neural cell adhesion molecule family of receptors, andit has been reported in learning disabilities, especially indyslexia. Interestingly, developmental difficulties involvingnotable delay in language acquisition are often observed inpatients with deletion of the 3p12 band.