Search PubMed⌕ Search

Biomedical subjects

J Mulley

Publications and source records attributed to J Mulley.

26 records · Page 2Linked to original sources
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↗
PubMed1991

Localisation of the MRX3 gene for non-specific X linked mental retardation.

A family is described with five affected males segregating a new gene for non-specific X linked mental retardation (MRX). Linkage analysis localised the gene at Xq28-qter. The maximum lod score was 2.89 with DXS52 (St14) at theta = 0.0. A recombinant was observed with DXS304 (U6.2) defining the proximal limit to the localisation. No evidence for linkage was determined using markers at several points along the remainder of the X chromosome, including the regions known to contain MRX1 and MRX2. This delineates the third gene for non-specific X linked mental retardation, MRX3.

Adult↗
PubMed1991

Non-specific X linked mental retardation.

Non-specific X linked mental retardation (MRX) is mental retardation in persons of normal physical appearance who have no recognisable features apart from a characteristic pedigree. Review of published reports shows that there is clinical variability in the degree of mental retardation within families and genetic heterogeneity, based on gene localisation, between families. We propose a classification based on genetic localisation and a set of minimal clinical features that should be recorded in the hope of identifying possible specific phenotypes.

Genetic Linkage↗
PubMed1991

Association of Treacher Collins syndrome and translocation 6p21.31/16p13.11: exclusion of the locus from these candidate regions.

Treacher Collins syndrome (TCS) is an autosomal dominant defect of craniofacial development which has not been chromosomally localized. We have identified a mother and two children who have TCS and also a balanced translocation t(6;16)(p21.31;p13.11), which suggested the possibility that the TCS locus might be located at one of the translocation breakpoints. These were defined by in-situ hybridization as 6p21.31 (by using loci in the HLA complex defined by the probes p45.1DP beta 003/HLA-DPB2 and pRS5.10/HLA class I chain) and 16p13.11 (by using probes pACHF1.3.2/D16S8 and VK45/D16S131). Pairwise and multipoint linkage analysis using localized chromosome 6 probes and chromosome 16 probes in 12 unrelated TCS families with multiple affected siblings excluded the TCS locus from proximity to both translocation breakpoints. These data were confirmed when a third affected child, who did not exhibit the translocation, was born to the mother.

Chromosome Banding↗
PubMed1989

Börjeson-Forssman-Lehmann syndrome: clinical manifestations and gene localization to Xq26-27.

We have studied 7 males in one family with mild/moderate intellectual handicap, long thick ears, deep-set eyes, small testes, and post pubertal gynecomastia. The affected males and some of the heterozygous females also had tapering fingers and short, widely spaced flexed toes. The pedigree demonstrates X-linked recessive inheritance. The clinical manifestations are similar to those described in the Börjeson-Forssman-Lehmann (BFL) syndrome but differ in the degree of mental handicap and the absence of "dwarfism" and microcepaly. This milder manifestation may represent either phenotypic or genotypic variation. DNA marker studies demonstrated linkage to the DXS86, DXS51, and F9 cluster at Xq26-q27. The maximum lod score was 2.1 with DXS51, at theta = 0.0. Definite recombinants were observed between DXS10 (at Xq26 but proximal to DXS86), DXS105 (at Xq27 but distal to F9), and BFL. Thus, the regional localization for BFL is Xq26-q27 between DXS10 and DXS105.

Abnormalities, Multiple↗
PubMedDate not supplied

Linkage between the fragile X and F9, DXS52 (St14), DXS98 (4D-8) and DXS105 (cX55.7).

Linkage data using the markers F9, DXS105 (cX55.7), DXS98 (4D-8) and DXS52 (St14) are presented from 22 kindreds segregating with the fragile X. Two-point linkage analysis was carried out taking into account cytogenetic results and penetrance classes defined by mental impairment status of mothers. Recombination frequencies (theta) corresponding to the maximum z scores (z) were obtained between F9 (z = 3.48, theta = 0.18), DXS105 (z = 5.06, theta = 0.07), DXS98 (z = 4.79, theta = 0.01) and DXS52 (z = 6.44, theta = 0.09) and the fragile X. Recombination frequencies between marker loci in fragile X families are also presented. These recombination frequencies need to be combined with those from other studies in order to determine the best estimates of map distances for use in genetic counselling, until markers closer to the fragile X, or at the fragile X, can be used. Most potential fra(X) heterozygotes were informative for flanking markers using the above 4 probes. Carrier risks were determined by 3-point analysis using informative flanking markers, taking into account cytogenetic results. Low level fra(X) expression occurred in 2 probable non-carriers; emphasising the need for extreme caution in the interpretation of low rates of expression.

Factor IX↗
PubMedDate not supplied

Localization of non-specific X-linked mental retardation genes.

Gene localization was determined by linkage analysis in 5 families with non-specific X-linked mental retardation (MRX) and were MRX1, Xp11.4-q21.31; MRX10, Xp21.3-p11.4; MRX11, Xp21.3-p11.22; MRX12, Xp21.3-q21.1; and MRX13, Xp22.3-q21.22. Four of these localizations cross the dystrophin brain promoter, a candidate locus for MRX. None of the affected individuals who were tested showed variation suggestive of a deletion. No consistent clinical features were observed between or within 4 of the 5 families. In MRX12, prematurity or low birth weight, hypotelorism and short stature were seen in several affected males. Heterozygote manifestations occurred in 3 families. There was no evidence to suggest involvement of the same gene in more than one family, nor to clinically separate these families into distinct genetic entities. Non-overlapping localizations for MRX1 and MRX10 demonstrate the existence of at least 2 separate loci among these 5 families.

Chromosome Mapping↗