Search PubMed⌕ Search

Biomedical subjects

A P Read

Publications and source records attributed to A P Read.

At least 55 records · Page 3Linked to original sources
PubMed1994

Diagnosis of adult polycystic kidney disease by genetic markers and ultrasonographic imaging in a voluntary family register.

Diagnosis of autosomal dominant adult polycystic kidney disease (APKD) is possible by ultrasonographic scanning (USS) or by using DNA markers linked to the PKD1 locus. Ultrasonography is complicated by the age dependent penetrance of the gene and linkage studies are subject to recombination errors owing to meiotic crossing over and locus heterogeneity. This study draws on data collected from a voluntary family register of APKD over 10 years. Records of 150 families were examined, ultrasound reports were obtained from 242 people at 50% prior risk, and 37 families were typed for DNA markers. The fraction of APKD resulting from loci unlinked to PKD1 (designated PKD2 here) was calculated at 2.94% (upper confidence limit 8.62%). Some subjects who were negative on initial scan later gave a positive scan, but there was no example of a definite gene carrier aged over 30 giving a negative scan. In families large enough for linkage analysis, most people who were at 50% prior risk could be given a final risk below 5% or above 95%, by using combined ultrasound and DNA studies.

Adolescent↗
PubMed1993

Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2.

Waardenburg syndrome (WS) is a combination of deafness and pigmentary disturbances, normally inherited as an autosomal dominant trait. The pathology involves neural crest derivatives, but WS is heterogeneous clinically and genetically. Some type I WS families show linkage with markers on distal 2q and in three cases the disease has been attributed to mutations in the PAX3 gene. PAX3 encodes a paired domain, a highly conserved octapeptide and probably also a paired-type homeodomain. Here we describe a further three PAX3 mutations which cause WS; one alters the octapeptide motif plus the presumed homeodomain; a second alters all three elements and the third alters the paired box alone. The latter occurs in a family with probable type 2 WS, a clinical variant usually considered not to be allelic with type 1 WS.

Amino Acid Sequence↗
PubMed1993

Mapping of the X linked form of hyper IgM syndrome (HIGM1)

X linked immunodeficiency with hyperimmunoglobulinaemia M (HIGM1), which is characterised by agammaglobulinaemia together with excess IgM production reflecting an impairment of the immunoglobulin heavy chain class switch of B lymphocytes, has been mapped to Xq26. We report multipoint linkage data in six families with HIGM1 which show that the most likely position for the gene is close to HPRT with a maximum lod score of 4.89. The finding of recombinations between HIGM1 and both HPRT and DXS42 implies that HIGM1 is not allelic to X linked lymphoproliferative disease. These data will be useful in genetic counselling in families and will also be useful in testing candidate genes.

Base Sequence↗
PubMed1992

Monozygotic twinning and Wiedemann-Beckwith syndrome.

Monozygotic (MZ) twinning occurs with relatively high frequency in Wiedemann-Beckwith syndrome (WBS). Ten sets of MZ twins with WBS have been reported. Nine of these have been female and in each case the twins were discordant for the WBS phenotype. The tenth set was male. They were concordant for WBS and both had a duplication of chromosome 15 which they shared in common with their phenotypically normal mother. The WBS gene has been assigned to the locus 11p15 and there appear to be several different genetic mechanisms involving this locus which all give rise to WBS. An imprinting effect for the WBS gene has been proposed because of the transmission of the gene preferentially through the maternal line in some large pedigrees. We describe two further sets of female MZ twins with WBS. One pair is concordant and one discordant for the condition. The possible genetic mechanisms involved in the expression of WBS are discussed, with particular reference to twinning, genomic imprinting and X-inactivation which is thought to be associated with the occurrence of MZ twinning in females.

Beckwith-Wiedemann Syndrome↗
PubMed1992

Recurrent Wiedemann-Beckwith syndrome with inversion of chromosome (11)(p11.2p15.5).

A baby with Wiedemann-Beckwith syndrome (WBS) and her phenotypically normal mother carried the same paracentric inversion, inv(11)(p11.2 15.5), in the short arm of chromosome 11. A fetus, sib of the affected baby, had the same inversion and ultrasound scan showed exomphalos. The maternal grandmother is clinically and cytogenetically normal. The pattern of affection in this family is consistent with the suggestion that WBS can be caused by lack of a maternally imprinted gene at 11p15.5, and that in this family the inversion disrupts that gene.

Beckwith-Wiedemann Syndrome↗
PubMed1992

Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene.

Waardenburg's syndrome (WS) is an autosomal dominant combination of deafness and pigmentary disturbances, probably caused by defective function of the embryonic neural crest. We have mapped one gene for WS to the distal part of chromosome 2. On the basis of their homologous chromosomal location, their close linkage to an alkaline phosphatase gene, and their related phenotype, we suggested that WS and the mouse mutant Splotch might be homologous. Splotch is caused by mutation in the mouse Pax-3 gene. This gene is one of a family of eight Pax genes known in mice which are involved in regulating embryonic development; each contains a highly conserved transcription control sequence, the paired box. Here we show that some families with WS have mutations in the human homologue of Pax-3. Mutations in a related gene, Pax-6, which, like Pax-3, has both a paired box and a paired-type homeobox sequence, cause the Small-eye mutation in mice and aniridia in man. Thus mutations in the Pax genes are important causes of human developmental defects.

Amino Acid Sequence↗
PubMed1992

Estimation of the male and female mutation rates in Duchenne muscular dystrophy (DMD).

We present the results of an international collaborative study aimed at estimating the ratio of male to female mutation rates in Duchenne muscular dystrophy based on the method of C. Müller and T. Grimm. With a sample size of 295, this ratio is found to be very close to 1, thus giving evidence for equal mutation rates in males and females in Duchenne muscular dystrophy.

Blotting, Southern↗
PubMed1992

Three DNA markers for hypophosphataemic rickets.

This paper presents three markers, 16D/E, pHMAI (DXS208), and CRI-L1391 (DXS274), that show close linkage for X-linked hypophosphataemic rickets (HYP). DXS274 is closely linked to HYP (theta max = 0.00, Zmax = 4.20), and DXS41 (99.6), (theta max = 0.00, Zmax = 5.20). Marker 16D/E maps distal to the disease locus (theta max = 0.05, Zmax = 3.11). The pHMAI probe recognises the same restriction fragment length polymorphism (RFLP) as 99.6. Multipoint analysis suggests that the most probable order of loci is Xpter-(DXS43, 16D/E)-HYP-DXS274-(DXS208, DXS41)-Xcen. The location of DXS274 distal to HYP cannot be excluded, as no recombinants were observed between DXS274 and HYP, or between DXS274 and DXS41/DXS208. One of the families contains a large number of recombinants, four of which are double recombinants. This most probably means that the disease in this family maps elsewhere on the X chromosome or on an autosome, indicating locus heterogeneity.

Blotting, Southern↗
PubMed1992

Is there a genetic basis for Fuchs' heterochromic uveitis? Discordance in monozygotic twins.

One pair, and probably two pairs, of monozygotic twins are reported with discordance for Fuchs' heterochromic uveitis (FHU). Regular Mendelian inheritance of this disease is now proved to be impossible. The heritability of FHU is low and may be zero. The possibility of any genetic predisposition to the disease and its association with 'simple' heterochromia are discussed.

Aged↗
PubMed1992

Fetus with unbalanced translocation involving chromosomes 2 and 11.

We report a fetus with an unbalanced translocation between chromosomes 2 and 11, the product of a paternal balanced reciprocal translocation, fetal karyotype 46, XX, -11, +der(11)t(2;11) (q35;q24.1)pat. The fetus had unusual facial features. The relevance of this case to mapping of the type I Waardenburg syndrome gene is discussed.

Abnormalities, Multiple↗
PubMed1991

New DNA markers in the Huntington's disease gene candidate region.

The search for the Huntington's disease (HD) gene has prompted construction of a complete long-range restriction map of a 2.5-Mb candidate region, distal to the DNA marker D4S10. To facilitate the procurement of cloned DNA from this candidate region, we have augmented the existing regional mapping panel of somatic cell hybrids with hybrid HHW1071 containing a t(4p16;12) chromosome from a patient with Wolf-Hirschhorn syndrome. This translocation maps between D4S180 and D4S127, subdividing the HD candidate region and setting a proximal limit to the Wolf-Hirschhorn syndrome region. Using the expanded mapping panel, we have regionally assigned 14 independently cloned cosmids, five proximal to the t(4;12) breakpoint in the same region as D4S10 and nine distal to the breakpoint. By a combination of overlap with previously mapped cosmids and pulsed-field gel analysis, each of these cosmids has been positioned on the long-range restriction map of 4p16.3, increasing the clone coverage of the candidate region to approximately 40%. Single-copy probes from mapped cosmids were used to identify eight new DNA polymorphisms spanning the HD candidate region. These new DNA markers should prove valuable for analysis of recombination and linkage disequilibrium in HD, as well as for preclinical diagnosis of the disorder.

Alleles↗
PubMed1991

X-linked and FSH dystrophies in one family.

A family is reported in which the father was affected by facioscapulohumeral muscular dystrophy FSHD. One son was affected by Duchenne muscular dystrophy (DMD). The second son died at the age of 3 yr of a severe primary muscle disease and it is suggested that this was the outcome of dual expression of the two conditions.

Adult↗
PubMed1991

The gene for Treacher Collins syndrome maps to the long arm of chromosome 5.

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. We have studied 12 unrelated TCS families with multiple affected individuals for linkage to five chromosome 5 markers. There is strong evidence demonstrating linkage to three of these markers. Multipoint linkage analysis places the mutation causing TCS in the interval between the gene for the glucocorticoid receptor and the anonymous marker D5S22, with a maximum multipoint lod score of 9.1.

Chromosome Mapping↗