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Finetti C.,Abteilung Neuropadiatrie | Utz N.,Klinik fur Radiologie und Neuroradiologie | Kruger S.,Gemeinschaftspraxis fur Humangenetik | Rosenbaum T.,Abteilung Neuropadiatrie
Monatsschrift fur Kinderheilkunde | Year: 2011

Pontocerebellar hypoplasia (PCH) type 2 is a rare autosomal recessive disorder, neuroradiologically characterized by a combination of cerebellar and pontine hypoplasia. Clinically it results in early retardation of psychomotor development, secondary progressive microcephaly and movement disorders. This article reports about a 3 1/2 - month-old patient in whom clinical and magnetic resonance imaging findings were indicative of PCH type 2 which was later confirmed by molecular genetic analyses. © 2011 Springer-Verlag.


Edener U.,University of Lubeck | Wollner J.,University of Lubeck | Hehr U.,University of Regensburg | Kohl Z.,Friedrich - Alexander - University, Erlangen - Nuremberg | And 6 more authors.
European Journal of Human Genetics | Year: 2010

Autosomal dominantly inherited spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders primarily affecting the cerebellum. Genetically, 26 different loci have been identified so far, although the corresponding gene has not yet been determined for 10 of them. Recently, mutations in the ATPase family gene 3-like 2 gene were presented to cause SCA type 28. To define the frequency of SCA28 mutations, we performed molecular genetic analyses in 140 unrelated familial cases with ataxia. Among other variations, we found a novel missense mutation at an evolutionarily conserved amino-acid position using a single-strand conformation polymorphism approach, followed by DNA sequencing. This amino-acid exchange p.E700K was detected in a four-generation German family and was not observed in a survey of 400 chromosomes from healthy control individuals. © 2010 Macmillan Publishers Limited All rights reserved.


Zuhlke C.,University of Lubeck | Kreuz F.,Gemeinschaftspraxis fur Humangenetik | Burk K.,University of Marburg
Nervenarzt | Year: 2011

Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological diseases affecting both the central and the peripheral nervous systems. They are characterized by autosomal recessive inheritance, progressive ataxia and degeneration of the cerebellum and spinal cord. Onset is generally before the third decade of life. The most frequent of these rare disorders in the Caucasian population is Friedreich's ataxia followed by ataxias with oculomotor apraxia. ARCAs are caused by mutations at specific loci but not every affected gene is known to date. Clinical diagnosis can be confirmed by ancillary tests (biochemical, neuroimaging and electrophysiological investigations) and mutation analyses if the causative gene has been identified. Correct clinical and genetic diagnosis is necessary for prognosis, genetic counseling and pharmacological treatment. For the majority of ARCAs a curative treatment is not available. © 2010 Springer-Verlag.


Spengler S.,RWTH Aachen | Begemann M.,RWTH Aachen | Ortiz Bruchle N.,RWTH Aachen | Baudis M.,University of Zurich | And 11 more authors.
Journal of Pediatrics | Year: 2012

Objective: To determine the contribution of submicroscopic chromosomal imbalances to the etiology of Silver-Russell syndrome (SRS) and SRS-like phenotypes. Study design: We performed molecular karyotyping in 41 patients with SRS or SRS-like features without known chromosome 7 and 11 defects using the Affymetrix SNP Array 6.0 system (Affymetrix, High Wycombe, United Kingdom). Results: In 8 patients, pathogenic copy number variations with sizes ranging from 672 kb to 9.158 Mb were identified. The deletions in 1q21, 15q26, 17p13, and 22q11 were associated with known microdeletion syndromes with overlapping features with SRS. The duplications in 22q13 and Xq25q27 represent unique novel copy number variations but have an obvious influence on the phenotype. In 5 additional patients, the pathogenetic relevance of the detected variants remained unclear. Conclusion: Pathogenic submicroscopic imbalances were detectable in a significant proportion of patients with short stature and features reminiscent of SRS. Therefore, molecular karyotyping should be implemented in routine diagnostics for growth-retarded patients with even slight dysmorphisms suggestive for SRS. Copyright © 2012 Mosby Inc.


Neuhann T.M.,MGZ Medizinisch Genetisches Zentrum | Stegerer A.,MGZ Medizinisch Genetisches Zentrum | Riess A.,Applied Genomics | Blair E.,University of Oxford | And 5 more authors.
American Journal of Medical Genetics, Part A | Year: 2015

ADAMTSL4 mutations seem to be the most common cause of isolated ectoplia lentis (EL) and thus are important concerning the differential diagnosis of connective tissue syndromes with EL as main feature. In this study, we describe an additional cohort of patients with apparently isolated EL. All underwent a detailed clinical exam with cardiac evaluation combined with ADAMTSL4 mutation analysis. Mutations were identified in 12/15 patients with EL. Besides the European founder mutation p. (Gln256Profs*38) we identified five further mutations not yet described in the literature: p. (Leu249Tyrfs*21), p. (Ala388Glyfs*8), p. (Arg746His), p. (Gly592Ser), and p. (Arg865His). Clinical evaluation showed common additional ocular features such as high myopia, but no major systemic findings. In particular: no dilatation of the aortic root was reported on. This report increases the total number of patients with ADAMTSL4 mutations reported on today and reviews in detail the clinical findings in all patients reported on to date demonstrate, that these patients have a mainly ocular phenotype. There are no consistent systemic findings. The differentiation between syndromic and isolated EL is crucial for the further surveillance, treatment, and counseling of these patients, especially in young children. © 2015 Wiley Periodicals, Inc.

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