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E Kremer

Publications and source records attributed to E Kremer.

8 recordsLinked to original sources
PubMed1992

Evidence of founder chromosomes in fragile X syndrome.

The mutation responsible for fragile X syndrome and myotonic dystrophy involves the amplification of a simple trinucleotide repeat sequence, which increases in successive generations of affected pedigrees accounting for increasing penetrance of both disorders. This common molecular basis suggests that the two diseases may share other genetic features, but whereas myotonic dystrophy exhibits a significant founder chromosome effect, fragile X syndrome apparently has a very high mutation frequency. By haplotype analysis of microsatellite markers which flank the fragile X unstable element, we have uncovered evidence of founder chromosomes of the fragile X 'mutation'. Disorders caused by heritable unstable elements may therefore exhibit common genetic properties including anticipation and founder chromosomes.

Base Sequence↗
PubMed1992

Fragile-X syndrome: unique genetics of the heritable unstable element.

The fragile site at Xq27.3 is an unstable microsatellite repeat, p(CCG)n. In fragile-X syndrome pedigrees, this sequence exhibits variable amplification, the length of which correlates with fragile-site expression. There is a direct relationship between increased p(CCG)n copy number and propensity for instability: individuals having large amplifications exhibit somatic variation due to increased instability. The instability of the p(CCG)n repeat, when transmitted through affected pedigrees, explains the unusual segregation patterns of fragile-X phenotype, referred to as the Sherman paradox. All individuals of fragile-X genotype were found (where testing was possible) to have a parent with amplified p(CCG)n repeat, indicating that few, if any, cases of fragile-X syndrome are not familial.

Blotting, Southern↗
PubMed1991

Hereditary unstable DNA: a new explanation for some old genetic questions?

Fragile X syndrome, associated with the fragile X chromosome, is the most common cause of familial mental retardation. The condition is characterised by a heritable DNA sequence that consists of an abnormal number of CCG repeats, and which is unstable in both mitosis and meiosis. We suggest that such heritable unstable DNA sequences could be present in other parts of the genome and that these might explain a number of genetic events that are not well understood in terms of classic genetic mechanisms. Such poorly explained observations include anticipation, incomplete penetrance, variable expression, and possibly imprinting, variegation, and multifactorial inheritance.

Chromosome Fragility↗
PubMed1991

Fragile X genotype characterized by an unstable region of DNA.

DNA sequences have been located at the fragile X site by in situ hybridization and by the mapping of breakpoints in two somatic cell hybrids that were constructed to break at the fragile site. These hybrids were found to have breakpoints in a common 5-kilobase Eco RI restriction fragment. When this fragment was used as a probe on the chromosomal DNA of normal and fragile X genotype individuals, alterations in the mobility of the sequences detected by the probe were found only in fragile X genotype DNA. These sequences were of an increased size in all fragile X individuals and varied within families, indicating that the region was unstable. This probe provides a means with which to analyze fragile X pedigrees and is a diagnostic reagent for the fragile X genotype.

Chromosome Mapping↗
PubMed1991

Fragile X syndrome: genetic localisation by linkage mapping of two microsatellite repeats FRAXAC1 and FRAXAC2 which immediately flank the fragile site.

We report the genetic localisation of the fragile site at Xq27.3 associated with fragile X syndrome. The position of the fragile site within the multipoint linkage map was determined using two polymorphic microsatellite AC repeat markers FRAXAC1 and FRAXAC2. These markers were physically located within 10 kilobases and on either side of the p(CCG)n repeat responsible for the fragile site. FRAXAC1 has five alleles with heterozygosity of 44% and is in strong linkage disequilibrium with FRAXAC2 which has eight alleles and a heterozygosity of 71%. No recombination was observed either between these markers in 40 normal CEPH pedigrees or with the fragile X in affected pedigrees. These markers provide the means for accurate diagnosis of the fragile X genotype in families by rapid polymerase chain reaction analysis and were used to position the fragile X within the multipoint map of the X chromosome to a position 3.7 cM distal to DXS297 and 1.2 cM proximal to DXS296.

Base Sequence↗
PubMed1978

Nephroptosis and kidney function.

We have investigated the influence of renal mobility on both renal blood flow and glomerular filtration, in order to evaluate its role as a potential intermediate cause of hypertension. In 25 untreated patients we compared between recumbent and upright position the relative change in the following five parameters: effective renal plasma flow (ERPF), glomerular filtration rate (GFR), renal mobility, peripheral plasma renin activity (PRA) and blood pressure. We found a positive correlation between the degree of renal mobility and an observed decrease in ERPF. On the other hand, no relation was found between the former and an observed decrease in GFR. The PRA appeared to rise following the decrease of the ERPF. These observations suggest that renal mobility adds to the orthostatic reduction in renal blood flow.

Adult↗