Moritz Meins - Academia.edu (original) (raw)

Papers by Moritz Meins

Research article Charcot-Marie-Tooth neuropathy type 2A: novel mutations in the mitofusin 2 gene ... more Research article Charcot-Marie-Tooth neuropathy type 2A: novel mutations in the mitofusin 2 gene (MFN2)

Journal of Medical Genetics, 2010

BMC medical genetics, Jan 8, 2006

Charcot-Marie-Tooth neuropathies are a group of genetically heterogeneous diseases of the periphe... more Charcot-Marie-Tooth neuropathies are a group of genetically heterogeneous diseases of the peripheral nervous system. Mutations in the MFN2 gene have been reported as the primary cause of Charcot-Marie-Tooth disease type 2A. Patients with the clinical diagnosis of Charcot-Marie-Tooth type 2 were screened using single strand conformation polymorphism (SSCP). All DNA samples showing band shifts in the SSCP analysis were amplified from genomic DNA and cycle sequenced. We analyzed a total of 73 unrelated patients with a clinical diagnosis of CMT 2. Overall, novel mutations were detected in 6 patients. c.380G>T (G127V), c.1128G>A (M376I), c.1040A>T (E347V), c.1403G>A (R468H), c.2113G>A (V705I), and c.2258_2259insT (L753fs). We confirmed a significant role of mutations in MFN2 in the pathogenesis of Charcot-Marie-Tooth disease type 2.

Investigative ophthalmology & visual science, 2001

To examine the role of Drosophila optomotor blind (omb)-related T-box genes in development of hum... more To examine the role of Drosophila optomotor blind (omb)-related T-box genes in development of human and mouse retina. Mouse Tbx2, Tbx3, and Tbx5 and human TBX2 cDNAs were isolated from retinal cDNA libraries by hybridization to the Drosophila omb gene. Gene expression patterns in developing retina were analyzed by in situ hybridization. TBX2/Tbx2, TBX3/Tbx3, and TBX5/Tbx5 were expressed asymmetrically across the embryonic neural retina with highest levels of mRNA within dorsal and peripheral retina. The dorsoventral gradient of TBX2 expression disappeared before the ganglion cell layer (GCL) formed. Its expression then became restricted to the inner neuroblastic retina and later to the GCL and inner nuclear layer (INL). The dorsal expression domains of TBX5/Tbx5 and TBX3/Tbx3 were maintained during formation of the GCL. As the retina matured, TBX3/Tbx3 expression was restricted to the INL, and TBX5/Tbx5 was expressed within the GCL. The expression pattern of TBX2, TBX3, and TBX5 wit...

Cytogenetic and Genome Research - CYTOGENET GENOME RES, 2002

RNA-binding proteins are involved in post-transcriptional processes like mRNA stabilization, post... more RNA-binding proteins are involved in post-transcriptional processes like mRNA stabilization, post-transcriptional modification, and transport and have been suggested to play an important role in developmental gene regulation. We report here the cloning and characterization of Brunol4, a novel mouse cDNA closely related to the elav-type family of genes encoding for RNA-binding proteins and a subfamily recently named after the bruno gene of Drosophila. Murine Brunol4 is localized near the centromere of chromosome 18. The cDNA sequence of Brunol4 is separated by 12 introns and the size of Brunol4 may be around 250 kb due to the large size of several introns. Brunol4 expression is detectable in the developing embryo and, later on becomes mainly restricted to cerebral structures, in particular the cerebellum where it persists in the adult organism. We predict a role of Brunol4 and the respective human homologue in differentiation and maintenance of neuronal structures.

Neuropediatrics, 2007

Alexander disease is a rare disorder of cerebral white matter due to a dysfunction of astrocytes.... more Alexander disease is a rare disorder of cerebral white matter due to a dysfunction of astrocytes. The most common infantile form presents as a megalencephalic leukodystrophy. Mutations of the GFAP gene, encoding Glial Fibrillary Acidic Protein, have been recognized as the cause of Alexander disease. Glial Fibrillary Acidic Protein is the major intermediate filament protein in astrocytes, its functional rod domain is conserved in sequence and structure among other intermediate filament proteins. We report here two cases of infantile Alexander disease with early onset and severe course, caused by DE NOVO mutations A364 V and Y366C. Both affected GFAP residues are part of a highly conserved coiled-coil trigger motif in the C-terminal end of segment 2B, probably required for the stability of intermediate filament molecules. Comparable effects are seen with mutations of the corresponding residues of the gene coding for keratin 14, another intermediate filament, this further supports the hypothesis that these positions of the trigger motif are generally critical for a normal function of intermediate filaments.

Molecular Reproduction and Development, 2007

Klinische Monatsblätter für Augenheilkunde, 1998

Lattice corneal dystrophy type I is one of the frequent forms of stromal dystrophies following au... more Lattice corneal dystrophy type I is one of the frequent forms of stromal dystrophies following autosomal dominant inheritance. The beta-IG-h3 gene encoding keratoepithelin on the long arm of chromosome 5 has recently been described as disease gene for lattice corneal dystrophy type I as well as for three other corneal dystrophies with autosomal dominant pattern of inheritance. Ten family members in three generations of a large family with autosomal dominant lattice corneal dystrophy were analyzed clinically by slit-lamp biomicroscopy. Mutation analysis in the beta-IG-h3 gene was carried out at the mRNA level by RT-PCR and cDNA sequencing. A heterozygous single-base substitution (417C--&amp;gt;T) in exon 4 of the beta-IG-h3 gene was detected predicting the replacement of arginine-124 by cysteine. Analysis of 10 family members showed perfect cosegregation of the mutation and lattice corneal dystrophy type I. The investigation excluded this mutation in one family member previously classified as potentially affected. The investigation confirmed autosomal dominant inheritance with complete penetrance in the family described. The mutation 417C--&amp;gt;T has already been found earlier in another family of different geographic origin. These results suggest a mutation hot spot at position 417. In addition, no evidence of genetic heterogeneity of lattice corneal dystrophy type I was detected. Molecular genetic analysis (in conjunction with genetic counselling) therefore may be useful in routine diagnostics as the confirmation of the diagnosis by histological examination is possible only after keratoplasty. The common pathomechanism in lattice corneal dystrophy type I may facilitate development of new therapeutic concepts; the easy accessibility of the target organ may provide new possibilities e.g. for gene therapy.

Journal of Medical Genetics, 2005

Journal of Medical Genetics, 2009

Human Mutation, 1999

Usher syndrome is a heterogeneous autosomal recessive trait and the most common cause of heredita... more Usher syndrome is a heterogeneous autosomal recessive trait and the most common cause of hereditary deaf-blindness. Usher syndrome type I (USH1) is characterised by profound congenital sensorineural hearing loss, vestibular dysfunction, and prepubertal onset of retinitis pigmentosa. Of the at least six different loci for USH1, USH1B maps on chromosome 11q13, and the MYO7A gene has been shown to be defective in USH1B. MYO7A encodes myosin VIIA, an unconventional myosin, and it consists of 48 coding exons. In this study, MYO7A was analysed in 34 unrelated Usher type I patients by single-strand conformation polymorphism analysis and direct sequencing. We identified a total of 12 novel and unique mutations, all single base changes. In addition, we found a previously reported nonsense mutation (C31X) on nine alleles of a total of six patients from Denmark.

Human Mutation, 2000

Usher syndrome (USH) is a clinically and genetically heterogeneous autosomal recessive disorder i... more Usher syndrome (USH) is a clinically and genetically heterogeneous autosomal recessive disorder in which sensorineural hearing loss is associated with retinitis pigmentosa. Usher syndrome type 1, the most severe form, is characterized by profound congenital deafness, vestibular dysfunction, and prepubertal onset of retinitis pigmentosa. Six different USH1 genes have so far been mapped, of which two have already been identified. MYO7A, encoding the unconventional myosin VIIA, underlies USH1B. Recently, the USH1C gene was shown to encode harmonin, a PDZ domain-containing protein. A previous screening of 18 unrelated USH1 patients, without a detected MYO7A mutation, for the three USH1C mutations described to date had demonstrated the presence of the 238-239insC mutation in the heterozygous state in four of them. A complete USH1C mutation screening in these four carriers of the 238-239insC mutation resulted in the detection of the second mutation in all the individuals, and the identification of three novel mutations, namely two splice site mutations (IVS1+1G>T and IVS5+1G>A) and a nonsense mutation (R31X). Thirty-one polymorphisms were detected in the USH1C gene. We observed that the E519D substitution is non-pathogenic, which is of particular interest for molecular diagnosis. Our analysis indicated that all the carriers of the 238-239insC mutation share a common haplotype. A different common haplotype was found in the two IVS1+1G>T carriers. Future studies of additional carriers and non-carriers should document the here proposed founder effect of these two mutations.

Human Mutation, 1994

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Human Molecular Genetics, 2008