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M Anvret

Publications and source records attributed to M Anvret.

At least 91 records · Page 5Linked to original sources
PubMed1994

Huntington disease without CAG expansion: phenocopies or errors in assignment?

Huntington disease (HD) has been shown to be associated with an expanded CAG repeat within a novel gene on 4p16.3 (IT15). A total of 30 of 1,022 affected persons (2.9% of our cohort) did not have an expanded CAG in the disease range. The reasons for not observing expansion in affected individuals are important for determining the sensitivity of using repeat length both for diagnosis of affected patients and for predictive testing programs and may have biological relevance for the understanding of the molecular mechanism underlying HD. Here we show that the majority (18) of the individuals with normal sized alleles represent misdiagnosis, sample mix-up, or clerical error. The remaining 12 patients represent possible phenocopies for HD. In at least four cases, family studies of these phenocopies excluded 4p16.3 as the region responsible for the phenotype. Mutations in the HD gene that are other than CAG expansion have not been excluded for the remaining eight cases; however, in as many as seven of these persons, retrospective review of these patients' clinical features identified characteristics not typical for HD. This study shows that on rare occasions mutations in other, as-yet-undefined genes can present with a clinical phenotype very similar to that of HD.

Adult↗
PubMed1993

Mutations of von Willebrand factor gene in families with von Willebrand disease in the Aland Islands.

Patients with von Willebrand disease in four families in the Aland Islands, including the original family that was described in 1926 by the Finnish physician von Willebrand, were screened for mutations in the Swedish "hot-spot" regions (exons 18, 28, 32, 43, and 45) of the von Willebrand factor gene. One cytosine deletion in exon 18 was detected in each of these families. Linkage analysis and genealogical studies suggest that the deletion present in these four families probably has an origin in common with the mutations in the Swedish patients. Apart from the deletion in exon 18, two close transitions (G-->A at S1263 and C-->T at P1266) in exon 28 on the same chromosome were identified in one individual who married into the original family and in his two children. The transitions could be due to a recombination between the von Willebrand factor gene and its pseudogene.

Adult↗
PubMed1993

Direct diagnosis of myotonic dystrophy with a disease-specific DNA marker.

BACKGROUND: Myotonic dystrophy is the most common inherited form of muscular dystrophy affecting adults. Its symptoms are not confined to muscle, and variability in their nature and in the patient's age at their onset can make diagnosis difficult. A specific unstable DNA sequence associated with myotonic dystrophy has recently been identified. We describe the use of a DNA probe (p5B1.4) that can detect this mutation directly, improving the accuracy and speed of diagnosis. METHODS: We analyzed DNA extracted from the peripheral-blood lymphocytes of 112 unrelated patients with myotonic dystrophy and their families, using molecular genetic techniques. Southern blot analysis and amplification with the polymerase chain reaction were used to determine the extent of expansion of the unstable DNA sequence. RESULTS: Probe p5B1.4 allowed direct identification of the myotonic dystrophy mutation in 108 of the 112 unrelated patients. In three families for whom the clinical and genetic data obtained with linked probes were ambiguous, the probe identified persons at risk for symptoms of this disorder and demonstrated that a possible sporadic case of myotonic dystrophy was familial. In one of these families the size of the unstable myotonic dystrophy-specific fragment decreased on transmission to offspring, who remained asymptomatic. CONCLUSIONS: The diagnosis of myotonic dystrophy is improved by the use of a probe that detects directly the mutation responsible for this disorder.

Adolescent↗
PubMed1993

X chromosome linkage studies in familial Rett syndrome.

Four families, each with two individuals affected by Rett Syndrome (RS), were analysed using restriction fragment length polymorphisms and microsatellite markers from the X chromosome. In two of the families, X-linked dominant inheritance of the RS defect from a germinally mosaic mother could be assumed. Therefore, maternal X chromosome markers showing discordant inheritance were used to exclude regions of the X chromosome as locations of the RS gene. Much of the short arm could be excluded, including regions containing three candidate genes, OTC, synapsin 1 and synaptophysin. Although most of the long arm was inherited in common it was possible to exclude a centromeric region. Inheritance of X chromosome markers is also presented for two families with affected aunt-niece pairs, one of which has not been previously studied at the DNA level.

Chromosome Mapping↗
PubMed1993

Molecular analysis of juvenile Huntington disease: the major influence on (CAG)n repeat length is the sex of the affected parent.

Juvenile Huntington disease (HD), characterised by onset of symptoms before the age of 20 with rigidity and intellectual decline, is associated with a predominance of affected fathers. In order to investigate the molecular basis for the observed parental effect, we have analysed the CAG trinucleotide repeat within the HD gene in 42 juvenile onset cases from 34 families. A highly significant correlation was found between the repeat length and age of onset (r = -0.86, p < 10(-7) and it was determined that the sex of transmitting parent was the major influence on CAG expansion leading to earlier onset. Neither the size of the parental upper allele, the age of parent at conception of juvenile onset child, nor the grandparental sex conferred a significant effect upon expansion. Affected sib pair analysis of CAG repeat length, however, revealed a high correlation (r = 0.91, p < 10(-7). Furthermore, analysis of nuclear and extended families showed a familial predisposition to juvenile onset disease. This study demonstrates that the sex of transmitting parent is the major influence on trinucleotide expansion and clinical features in juvenile Huntington disease.

Adolescent↗
PubMed1993

Larger expansions of the CTG repeat in muscle compared to lymphocytes from patients with myotonic dystrophy.

The discovery that there is an expansion of a CTG repeat underlying myotonic dystrophy has led to new approaches in diagnosis and genetic counselling for this disorder. The size of the expansion correlates to a reasonable degree with the clinical symptoms within a given family. We report comparisons of the length of the expansion seen in lymphocytes and muscle samples from eight patients. In all cases the length of the expansion seen in DNA isolated from muscle was larger than that seen in lymphocytes from the same patient. There was no progression of the expansion over a period of 10-15 years in muscle samples from two of these patients even though there had been significant progression of the severity of symptoms during that time.

Adult↗
PubMed1993

DNA analysis of distinct populations suggests multiple origins for the mutation causing Huntington disease.

Results of association studies can be significantly biased if the ancestry of the control population is not similar to that of the affected population. One approach to overcome such a bias is to use distinct populations where controls and affected individuals are likely to be of similar descent. We have examined homogeneous populations of French, Danish and Swedish ancestry for nonrandom allelic association between Huntington disease (HD) and several markers previously shown to be in association with HD. No evidence for nonrandom allelic association between HD and these markers was shown in these populations. The demonstration of association in a United Kingdom (UK) sample of similar size, and lack of significant differences in allele frequencies between the French, Danish, Swedish and UK populations suggested that the absence of association was not predominantly a consequence of allele frequencies or sample size. To investigate further the number of potential HD chromosomes, DNA haplotypes were constructed for the Danish, French, Swedish and UK populations. The minimum of two HD haplotypes observed in each of the French, Danish and Swedish populations, compared to the one haplotype in the UK population of a similar size, is an important factor accounting for the absence of association between HD and the DNA markers in these populations. Furthermore, these data are in favour of multiple independent origins for the mutation causing HD.

Alleles↗
PubMed1993

Hemophilia B in a 46,XX female probably caused by non-random X inactivation.

A female whose father had severe hemophilia B was found to have a factor IX activity of about 1%. No chromosomal abnormality could be detected and DNA analysis gave no indications of deletions or mutations of Taq I cleavage sites in the factor IX gene. Analysis of the methylation pattern of locus DXS255 indicates that the expression of hemophilia B in this patient is caused by non-random X inactivation.

Blotting, Southern↗
PubMed1993

Genetic carrier detection in Norwegian families with acute intermittent porphyria.

Early detection of carriers of acute intermittent porphyria (AIP) is of great value as an assistance for correct diagnosis and prevention of attacks. In order to complement traditional biochemical methods, restriction fragment length polymorphism (RFLP) studies as well as analysis for a previously identified point mutation were included in a study of three Norwegian AIP families. Several asymptomatic carriers could be identified, and the study thus demonstrates the usefulness of the combination of biochemical and genetic analysis.

Cross Reactions↗
PubMed1992

Prader-Willi syndrome in a brother and sister without cytogenetic or detectable molecular genetic abnormality at chromosome 15q11q13.

We report on a 12-year-old boy and his 7-year-old sister with the Prader-Willi syndrome. They both had severe initial hypotonia with feeding problems and later developed an increasing appetite. Both sibs have almond-shaped eyes, triangular mouth, hypogonadism, retarded growth, and mental retardation. An older brother suffered from severe hypotonia and died at 7 days of age. The children have normal chromosomes by high-resolution technique and have inherited the same chromosomes 15 short arm polymorphisms from their parents. The family was informative for one of four DNA markers specific for the 15q11q13 region. No deletion was found using this marker. The parents were healthy and unrelated. Autosomal recessive inheritance or a paternally inherited submicroscopic deletion are possible explanations for the sib occurrence in this family.

Adult↗
PubMed1992

Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy.

Myotonic dystrophy (DM) is the most common form of adult muscular dystrophy, with a prevalence of 2-14 per 100,000 individuals. The disease is characterized by progressive muscle weakness and sustained muscle contraction, often with a wide range of accompanying symptoms. The age at onset and severity of the disease show extreme variation, both within and between families. Despite its clinical variability, this dominant condition segregates as a single locus at chromosome 19q13.3 in every population studied. It is flanked by the tightly linked genetic markers ERCC1 proximally and D19S51 distally; these define the DM critical region. We report the isolation of an expressed sequence from this region which detects a DNA fragment that is larger in affected individuals than in normal siblings or unaffected controls. The size of this fragment varies between affected siblings, and increases in size through generations in parallel with increasing severity of the disease. We postulate that this unstable DNA sequence is the molecular feature that underlies DM.

Chromosomes, Human, Pair 19↗