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Hamburg, Germany

Stettner G.M.,University of Gottingen | Shoukier M.,University of Gottingen | Hoger C.,University of Gottingen | Brockmann K.,University of Gottingen | And 2 more authors.
American Journal of Medical Genetics, Part A | Year: 2011

Alterations of the Fragile Mental Retardation 2 gene (FMR2, synonym AFF2) can result in non-specific, mild to borderline X-linked intellectual disability (XLID), and behavioral problems. The well-known molecular pathomechanism of this condition, also referred to as FRAXE, is a (CCG) n trinucleotide repeat expansion which leads to silencing of the FMR2 gene. However, deletions within the FMR2 gene may also be causative of the disorder. Here, we report on two brothers diagnosed with FRAXE in whom a small deletion in the FMR2 gene was detected by whole genome array comparative genomic hybridization (CGH). The deletion was also present in their clinically healthy mother and maternal uncle who was similarly affected, but not in a healthy older brother of the two patients. Our observation demonstrates that FMR2 gene deletions may contribute to the FRAXE phenotype. Therefore, we suggest that screening for FMR2 gene deletions using array CGH should be considered in patients with non-specific XLID and absent trinucleotide expansion. © 2011 Wiley-Liss, Inc. Source

Shoukier M.,University of Gottingen | Wickert J.,University of Gottingen | Schroder J.,University of Gottingen | Bartels I.,University of Gottingen | And 8 more authors.
American Journal of Medical Genetics, Part A | Year: 2012

Interstitial deletions of the proximal chromosome 16q are rare. To date, only six cases with molecularly well-characterized microdeletions within this chromosomal region have been described. We report on a patient with severe psychomotor delay, dysmorphic features, microcephaly and hypoplasia of the corpus callosum, epilepsy, a heart defect, and pronounced muscular hypotonia. Array comparative genomic hybridization (aCGH) revealed that the patient's features were likely caused by a 4.7Mb de novo deletion on chromosome 16q12.1q12.2, which was confirmed by quantitative real-time PCR (qPCR). The psychomotor delay and craniofacial dysmorphism are more severe in our patient than previously reported patients. Unmasked recessive mutations in the ZNF423 and FTO genes on the remaining allele were excluded as the putative cause for this severe phenotype. In conclusion, the phenotypic spectrum of microdeletions in 16q12 is broad and comprises variable degrees of psychomotor delay and intellectual disability, craniofacial anomalies, and additional features, including heart defects, brain malformations, and limb anomalies. © 2011 Wiley Periodicals, Inc. Source

Kionke J.,Universitatsklinikum Hamburg Eppendorf | Grundmann T.,Hals Nasen Ohren Abteilung | Bullmann C.,Zentrum fur Endokrinologie | Auber B.,MVZ genteQ GmbH
Internist | Year: 2012

A 27-year-old female patient presented with multiple lipomas and cavernous hemangiomas of the skin, hemangioma of the parotid gland, polyps of the gastrointestinal tract and endometrial carcinoma. After 1 year the patient presented with papillary thyroid carcinoma and a diagnosis of Cowden syndrome (CS) was made. Genetic testing revealed a pathogenic PTEN gene mutation. Hereditary tumor syndromes, such as CS are underdiagnosed. Clinical management can be adjusted to the needs of CS patients only if an early diagnosis is made. In CS the risk for thyroid, breast and endometrial cancer is severely increased. © Springer-Verlag 2012. Source

Abdollahpour H.,University of Hamburg | Abdollahpour H.,MVZ genteQ GmbH | Alawi M.,University of Hamburg | Alawi M.,Heinrich Pette Institute | And 6 more authors.
European Journal of Human Genetics | Year: 2015

The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160-1161delCA (p.(Thr387Argfs∗30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome. © 2015 Macmillan Publishers Limited All rights reserved. Source

Kortum F.,Universitatsklinikum Hamburg Eppendorf | Abdollahpour H.,Universitatsklinikum Hamburg Eppendorf | Abdollahpour H.,MVZ genteQ GmbH | Alawi M.,Universitatsklinikum Hamburg Eppendorf | And 8 more authors.
Medizinische Genetik | Year: 2014

Background. Whole exome sequencing (WES) is the state-of-the-art method for identification of pathogenic mutations in patients with a Mendelian disorder. WES comprehensively covers the coding sequence of the genome and is a fast and cost-effective technique. Purpose. As most of the technical difficulties have been overcome for WES, the major issue is data processing and analysis to find the pathogenic sequence variation among tens of thousands of sequence changes. Bioinformatic analysis pipelines for filtering sequence variants have to be adapted according to the patients and family members examined by WES and the most likely inheritance pattern underlying the disease. Possible approaches. Based on 4 cases, different variant prioritization strategies which led to identification of the most likely causative changes in the index patients are described. © 2014 Springer-Verlag. Source

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