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Hamburg, Germany

Neuhann T.M.,Humangenetik
Klinische Monatsblatter fur Augenheilkunde | Year: 2015

If not due to trauma, ectopia lentis is usually caused genetically. It is a main symptom of several syndromal disorders such as Marfan syndrome or homocystinuria. Also other connective tissue disorders convey an elevated risk for ectopia lentis. Isolated ectopia lentis is frequently caused by genetic alterations as well, most commonly due to mutations in ADAMTSL4. Depending on the molecular basis, the consequences for the management of patients may differ significantly: On the one hand, possible accompanying symptoms may require a specific surveillance and treatment. Also, the risk for other family members to develop ectopia lentis or accompanying symptoms can only be determined if the genetic cause and thus inheritance pattern are known. This review describes the different types and genetic causes of syndromal and isolated ectopia lentis as well as possible consequences for the patients; also it presents a sensible algorithm for the molecular diagnostic approach. © Georg Thieme Verlag KG Stuttgart, New York. Source

Michels G.,University of Cologne | Erdmann E.,University of Cologne | Schmidt W.,Humangenetik | Frank K.F.,University of Cologne | Pfister R.,University of Cologne
Internal Medicine | Year: 2012

Birt-Hogg-Dubé syndrome is a rare autosomal dominant condition caused by a germline mutation in the folliculin gene, which is characterized by skin fibrofolliculomas, multiple lung cysts and renal cancer. The clinical expression of the syndrome is highly variable, with recurrent pneumothoraces due to ruptured lung cysts in many cases. We report a patient with pneumomediastinum and cervico-facial emphysema after severe coughing without pneumothorax, skin lesions or renal tumour, but a striking family history of lung abnormalities. © 2012 The Japanese Society of Internal Medicine. Source

Clayton P.,University College London | Fischer B.,Charite - Medical University of Berlin | Mann A.,University College London | Mansour S.,University of London | And 20 more authors.
Nucleus | Year: 2010

The lamin B receptor (LBR) is an inner nuclear membrane protein with a structural function interacting with chromatin and lamins, and an enzymatic function as a sterol reductase. Heterozygous LBR mutations cause nuclear hyposegmentation in neutrophils (Pelger anomaly), while homozygous mutations cause prenatal death with skeletal defects and abnormal sterol metabolism (Greenberg dysplasia). It has remained unclear whether the lethality in Greenberg dysplasia is due to cholesterol defects or altered nuclear morphology. To answer this question we characterized two LBR missense mutations and showed that they cause Greenberg dysplasia. Both mutations affect residues that are evolutionary conserved among sterol reductases. In contrast to wildtype LBR, both mutations failed to rescue C14 sterol reductase deficient yeast, indicating an enzymatic defect. We found no Pelger anomaly in the carrier parent excluding marked effects on nuclear structure. We studied Lbr in mouse embryos and demonstrate expression in skin and the developing skeletal system consistent with sites of histological changes in Greenberg dysplasia. Unexpectedly we found in disease-relevant cell types not only nuclear but also cytoplasmatic LBR localization. The cytoplasmatic LBR staining co-localized with ER-markers and is thus consistent with the sites of endogeneous sterol synthesis. We conclude that LBR missense mutations can abolish sterol reductase activity, causing lethal Greenberg dysplasia but not Pelger anomaly. The findings separate the metabolic from the structural function and indicate that the sterol reductase activity is essential for human intrauterine development. © 2010 Landes Bioscience. Source

Gilly B.,Klinik fur Dermatologie und Allergologie | Unholzer A.,Klinik fur Dermatologie und Allergologie | Strobl-Wildemann G.,Humangenetik | Haas C.,Pathologisches Institute | And 2 more authors.
Hautarzt | Year: 2013

Muir-Torre syndrome (MTS) is a rare phenotypic variant of hereditary non-polyposis colorectal carcinoma (HNPCC, Lynch syndrome), in which patients, in addition to visceral carcinomas, develop skin tumors. Multiple keratoacanthomas and basal cell carcinomas with sebocytic differentiation are characteristic as well as multiple benign and malignant tumors of the sebaceous glands, such as sebaceous adenoma, sebaceous epithelioma (sebaceoma) and sebaceous carcinoma. Particularly Cystic tumors of the sebaceous glands are especially suggestive of MTS. In genetically predisposed persons, cutaneous and visceral tumors are diagnosed at an average age of 53 years. Here we present an interesting case of a 65-year-old man in whom molecular genetic tests revealed a novel mutation in the MSH2 gene, leading to a frame shift within the gene. © 2012 Springer-Verlag Berlin Heidelberg. Source

Background: In a review of the literature in 2000 the different cytogenetic aspects of spontaneous miscarriages were well documented. This review also included the spontaneous miscarriage results of one large German study published in 1990. However, to our knowledge there are no new data on spontaneous miscarriages in the German population. Therefore, the aim of the present retrospective large study was to find out the incidence and types of chromosome aberrations in an unselected series of spontaneous miscarriages in the German population, and whether our more recent results were different to data published previously. In case of culture failure we implemented a quantitative fluorescent polymerase chain reaction (QF-PCR) for chromosomes 13, 18, 21, X and Y. Results: In the present German retrospective study cytogenetic analysis (CA) was attempted on 534 spontaneous miscarriages between weeks 7 and 34 of gestation, being successful in 73% (390/534) of them. Two hundred and thirty-seven of the cases (61%, 237/390) were chromosomally abnormal. Trisomy was the most common chromosome aberration and accounted for 53% (125/237) of the aberrant karyotypes. A multiple aneuploidy was observed in 7% (17/237) of the aberrant karyotypes. Chromosomes 16, 22, 15 and 21 were found most frequently involved in aneuploidies. Fifty-four cases (23%, 54/237) with a polyploidy were found in the present study. Single unbalanced structural chromosome aberrations accounted for 4% (10/237) of the aberrant karyotypes. Eleven samples (5%, 11/237) displayed a variety of numerical and/or structural chromosome aberrations. One hundred and forty-four spontaneous miscarriages (27%, 144/534) failed to grow in culture. A total of 27 cases were analysed by QF-PCR for chromosomes 13, 18, 21, X and Y, being informative in all cases. Conclusion: In our German retrospective large study of spontaneous miscarriages, the incidence and types of chromosome aberrations by CA are within the reported range of other studies published previously before and after 2000. Therefore, we can conclude that cytogenetic aspects of spontaneous miscarriages have not changed over the years. Additionally 8 of 27 cases (30%) without cell growth showed a numerical chromosome aberration by QF-PCR. Therefore QF-PCR played an important role as a supplementary test when culture failure occurred. © 2014 Jenderny; licensee BioMed Central Ltd. Source

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