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M Warburg

Publications and source records attributed to M Warburg.

At least 19 recordsLinked to original sources
PubMed1992

X-linked retinitis pigmentosa: new map studies of XLRP2, and a possible human centromere effect.

A new large Danish family with X-linked retinitis pigmentosa was studied for linkage analysis. Carrier diagnosis was performed using full-field electro-retinogram combined with a careful fundus examination. Multipoint linkage analysis, employing DNA markers from the proximal short arm of the X chromosome and the cytogenetic centromere marker, revealed the highest location score distally to DXS255 and proximal to the ornithine carbamoyl transferase locus. In comparison with the first Danish family that we studied, the pericentromeric recombination fraction was increased; it is speculated that the observed difference in genetic distances from the centromere in the 2 Danish families is correlated with a difference in the size and location of the centromeric heterochromatin.

Adult↗
PubMed1992

Isolation of a candidate gene for Norrie disease by positional cloning.

The gene for Norrie disease, an X-linked disorder characterized by progressive atrophy of the eyes, mental disturbances and deafness, has been mapped to chromosome Xp11.4 close to DXS7 and the monoamine oxidase (MAO) genes. By subcloning a YAC with a 640 kilobases (kb) insert which spans the DXS7-MAOB interval we have generated a cosmid contig which extends 250 kb beyond the MAOB gene. With one of these cosmids, microdeletions were detected in several patients with Norrie disease. Screening of cDNA libraries has enabled us to isolate and sequence a likely candidate gene for Norrie disease which is expressed in retina, choroid and fetal brain. No homologous sequences were found in DNA and protein databases indicating that this cDNA is part of a gene encoding a 'pioneer' protein.

Adult↗
PubMed1992

Mutations in the candidate gene for Norrie disease.

Recently, we and others have isolated a candidate gene for X linked Norrie disease (ND) which was found to be deleted or disrupted in several patients. As a prerequisite for the identification of point mutations in the ND gene we have established the exon-intron structure of this gene. In 17 unrelated patients and 15 controls, PCR products derived from the promoter region, exons 1 and 2 as well as the coding part of exon 3 were analysed with the single strand conformation polymorphism (SSCP) technique. In 12 patients altered PCR fragments were detected which were studied in detail by direct sequencing. Eleven different mutations were found, and all but one are likely to give rise to significant structural changes in the predicted protein. These findings, and the absence of functionally relevant base changes in healthy controls, emphasize the causal role of this candidate gene in Norrie disease and pave the way for reliable diagnosis and carrier detection.

Base Sequence↗
PubMed1992

Ring chromosome 22 and neurofibromatosis.

Variable constitutional mosaicism, mos45,XY,-22/46,XY,-22,+mar/46,XY,-22,+r(22)/47,XY,-22,+r(22)+mar/ 47, XY,-22,+r(22)*2, was found in PHA-stimulated peripheral blood, in a lymphoblastoid cell line and in cultured skin fibroblasts from a mentally retarded patient with neurofibromatosis. Both the ring chromosome and the small extra marker chromosome stained positively by in situ hybridization with a chromosome 14/22-specific alphoid repeat probe. DNA dosage analysis showed constitutional loss of one copy of the arylsulfatase A gene (ARSA), consistent with its terminal location on 22q. There was no evidence of constitutional loss of D22S1 or D22S28 which flank the neurofibromatosis type 2 (NF2) locus. Analysis of two DNA samples from a skin neurofibroma indicated retainment of two copies of D22S1, whereas the results were ambiguous with respect to tumor-specific loss of one copy of D22S28. It is suggested that the development of neurofibromatosis of unclear type in two r(22) carriers might be associated with somatic mutation of the NF2 locus due to instability of the ring chromosome(s), and in analogy, that somatic mutation of either NF1 or NF2 may account for some cases of neurofibromatosis which do not meet the criteria of either NF1 or NF2. The occurrence of seminoma in the proband may be fortuitous, but could also be due to the presence of a seminoma-associated locus on chromosome 22.

Adult↗
PubMed1992

Autosomal dominant congenital cataract; linkage relations; clinical and genetic heterogeneity.

Congenital cataract is a heterogeneous disorder. Approximately one third of the cases are hereditary. A large family with autosomal dominant congenital cataract is described here. Clinical examinations showed variable expressivity, but all affected persons were eventually operated, most of them in the first or second decade of life. Linkage relations with a number of polymorphic marker systems were studied, all of them being negative. Among the 21 systems studied were Fy, HP, D16S4 and CRYG. The present autosomal dominant congenital cataract is termed the Volkman cataract, after the ancestor in the pedigree, and is genotypically different from the Marner cataract found in another large Danish pedigree.

Cataract↗
PubMed1992

Visual impairment in Nordic children. I. Nordic registers and prevalence data.

A Nordic study group of ophthalmologists, NORDSYN, has compiled data from registers in Denmark, Finland, Iceland and Norway of 2527 visually impaired children. Each record contains the following information: sex, year of birth, year of registration, classification of visual impairment, ocular diagnosis, systemic diagnosis, aetiology and evt. additional impairments. The ocular diagnoses were compiled into groups, and coding systems for aetiology and additional impairment were developed. The sex distribution revealed a dominance of males compared to the general population at the same age. Cases with non-genetic aetiology showed--through to a lesser extent--the same relative preponderance of males. The diseases in males caused by x-linked genetic factors do, therefore, not fully explain the sex distribution observed in the study. The national prevalences for registration of childhood blindness (WHO-definition: best corrected visual acuity in the best eye less than 3/60 or visual field less than 10 degrees around fixation for the ages 0-15 years) are per 100,000 child-population aged 0-15 years: Denmark 41, Finland 15, Iceland 19 and Norway 15. The differences are primarily presumed to be due to varying efficiency in registration. The proportion of visually impaired children with an additional mobility, hearing or mental impairment is between one-third and one-half of the national materials, thus indicating the need for interdisciplinary tracing of and care for the visually impaired child. This study documents the need of uniform routines for data classification of visually impaired children. The quality of the data in the present study calls for caution in the interpretation of the prevalence estimates. Incidence studies are being prepared to obtain information on whether the amount and causes of visual impairment in children with or without multiple impairments are changing.

Adolescent↗
PubMed1992

Clinical reinvestigation and linkage analysis in the family with Episkopi blindness (Norrie disease).

We present the results of a clinical and genetic reinvestigation of the Cypriot family affected by an X chromosomally inherited eye disease originally published by Taylor et al, who coined the term Episkopi blindness. The pedigree was extended to 160 members, including 16 affected males out of 48 males at risk for the disease, most of whom were seen by one of us (PA). Affected males are blind with no associated symptoms and apparently are not mentally retarded. Thirty-nine family members agreed to blood sampling for genetic investigations. RFLP analysis was performed using probes from the region known to be deleted in some Norrie patients and polymorphic markers (DXS77, DXS7, MAOA, DXS255) from the proximal short arm of the X chromosome. There was no deletion for any of the probes in the affected males. Linkage analysis yielded positive lod scores for all informative markers (Z (DXS255, theta = 0) = 6.54, Z (MAOA, theta = 0) = 2.23, Z (DXS7, theta = 0) = 2.13). Thus, the conclusion that Episkopi blindness and Norrie disease (NDP, MIM *310600) are the same entity based on clinical evidence is now reinforced by gene mapping.

Adult↗
PubMed1992

Update of sporadic microphthalmos and coloboma. Non-inherited anomalies.

The majority of patients with microphthalmos and colobomas have genetic disorders. This is a survey of non-inherited, sporadic microphthalmos. Such cases may occur in the Goldenhar, CHARGE and VATER associations; it may also be due to teratological agents, for instance maternal ingestion of drugs, maternal infection, fever or irradiation. In these cases it is possible that neural crest cell development is abnormal. Some drugs, for instance retinoic acid are regulators of Hox genes which control an ordered sequence of differentiation; coloboma or microphthalmos may appear if deregulation occurs. Large choristomas of the anterior segment of the eye may be associated with microphthalmos or anophthalmos. Encephaloceles or orbital tumours may deform the growing eye and are another cause of non-inherited microphthalmos.

Abnormalities, Drug-Induced↗
PubMed1991

Deletion mapping of a retinal cone-rod dystrophy: assignment to 18q211.

Deletion of 18q211 was observed in a mentally retarded young man with electrophysiologically demonstrated cone-rod dystrophy, present since childhood. He had hypogonadism and a central postsynaptic hearing impairment. This is the first case of a chromosome deletion in a patient with a cone-rod dystrophy. Three patients with more distal deletions on chromosome 18 did not present retinal dystrophies. We suggest that one of the loci for cone-rod dystrophy may be located on chromosome 18 at q211-213. Reports of similar findings will be necessary for confirmation of this assumption.

Abnormalities, Multiple↗
PubMed1991

[Development of sight].

It is possible to measure the visual acuity in infants born eight weeks before term and later. It is correct when parents say that infants look at them and know them when they are only a few weeks of age. At birth, vision is only approximately 1/60, but in the course of the first three months, vision increases to 6/60 or 6/36. Simultaneously, the retina, optic nerve and central nervous system develop so that the picture which the infant registers on the retina may be interpreted. At the age of 3-4 months, binocular vision, accommodation and appreciation of depth commence. Eye movements develop at the same time. At first, these are jerky and inaccurate but, at the age of six months, movements are smooth. By this time, the child can maintain fixation and can adjust the eyes to new fields without error. The child's visual interest matures simultaneously. The best possible visual acuity and complete maturation of the visual cortex of the brain are achieved just before puberty. The development of sight during the first months is of critical significance for visual function during the remainder of life.

Evoked Potentials, Visual↗
PubMed1990

The Cohen syndrome. Retinal lesions and granulocytopenia.

A patient with the Cohen syndrome is described and the literature is reviewed. Electroretinography (ERG) showed that the patient had a tapeto-retinal degeneration. The authors believe that a retinitis pigmentosa-like phenotype is an obligatory sign in patients with the Cohen syndrome. Assessment of a tapeto-retinal dystrophy by electroretinography, however, is often not available for mentally retarded persons. The authors' patient also had granulocytopenia. This was previously described in Finnish patients with Cohen's syndrome. They speculate that this sign is more prevalent in the disorder than would appear from the literature. Alternatively, there may be a type I Cohen syndrome with granulocytopenia and a type II without.

Abnormalities, Multiple↗
PubMed1990

The Yemenite deaf-blind hypopigmentation syndrome. A new oculo-dermato-auditory syndrome.

We have seen a Yemenite sister and brother with cutaneous hypomelanotic and pigmented spots and patches, microcornea, coloboma, severe hearing loss and normal karyotypes. Histopathological examinations of the skin showed absent melanocytes in the depigmented areas; in the normal and hyperpigmented skin there was abundant melanotic pigment. Similar patients have not been described previously, but there are corresponding mutations in mice and rats.

Abnormalities, Multiple↗
PubMed1989

Dystrophy: a revised definition.

Dystrophy is defined as the process and consequences of hereditary progressive affections of specific cells in one or more tissues that initially show a normal function. The term abiotrophy was previously applied to these lesions, but has gone out of use. Degeneration is an equivocal term used for both acquired and hereditary disorders. Aging may or may not be considered as dystrophy. Dysplasias or dyshistogeneses are different from dystrophies. Dyshistogenetic tissues present with abnormal structure and function at birth in contrast to dystrophies, which are genetically programmed for later onset.

Aging↗