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R Mountford

Publications and source records attributed to R Mountford.

At least 19 recordsLinked to original sources
PubMed2003

Nail patella syndrome: a review of the phenotype aided by developmental biology.

Nail patella syndrome (NPS) is an autosomal dominant condition affecting the nails, skeletal system, kidneys, and eyes. Skeletal features include absent or hypoplastic patellae, patella dislocations, elbow abnormalities, talipes, and iliac horns on x ray. Kidney involvement may lead to renal failure and there is also a risk of glaucoma. There is marked inter- and intrafamilial variability. The results of a British study involving 123 NPS patients are compared with previously published studies and it is suggested that neurological and vasomotor symptoms are also part of the NPS phenotype. In addition, the first data on the incidence of glaucoma and gastrointestinal (GI) symptoms in NPS are presented. NPS is caused by loss of function mutations in the transcription factor LMX1B at 9q34. The expansion of the clinical phenotype is supported by the role of LMX1B during development.

Adolescent↗
PubMed2002

The N34S mutation of SPINK1 (PSTI) is associated with a familial pattern of idiopathic chronic pancreatitis but does not cause the disease.

BACKGROUND: Mutations in the PRSS1 gene explain most occurrences of hereditary pancreatitis (HP) but many HP families have no PRSS1 mutation. Recently, an association between the mutation N34S in the pancreatic secretory trypsin inhibitor (SPINK1 or PSTI) gene and idiopathic chronic pancreatitis (ICP) was reported. It is unclear whether the N34S mutation is a cause of pancreatitis per se, whether it modifies the disease, or whether it is a marker of the disease. PATIENTS AND METHODS: A total of 327 individuals from 217 families affected by pancreatitis were tested: 152 from families with HP, 108 from families with ICP, and 67 with alcohol related CP (ACP). Seven patients with ICP had a family history of pancreatitis but no evidence of autosomal dominant disease (f-ICP) compared with 87 patients with true ICP (t-ICP). Two hundred controls were also tested for the N34S mutation. The findings were related to clinical outcome. RESULTS: The N34S mutation was carried by five controls (2.5%; allele frequency 1.25%), 11/87 (13%) t-ICP patients (p=0.0013 v controls), and 6/7 (86%) affected (p<0.0001 v controls) and 1/9 (11%) unaffected f-ICP cases. N34S was found in 4/108 affected HP patients (p=0.724 v controls), in 3/27 (11%) with wild-type and in 1/81 (1%) with mutant PRSS1, and 4/67 ACP patients (all p>0.05 v controls). The presence of the N34S mutation was not associated with early disease onset or disease severity. CONCLUSIONS: The prevalence of the N34S mutation was increased in patients with ICP and was greatest in f-ICP cases. Segregation of the N34S mutation in families with pancreatitis is unexplained and points to a complex association between N34S and another putative pancreatitis related gene.

Adult↗
PubMed2001

A new polymorphism for the RI22H mutation in hereditary pancreatitis.

BACKGROUND AND AIMS: Hereditary pancreatitis (HP) is a rare form of recurrent acute and chronic pancreatitis. Mutations in the cationic trypsinogen (protease serine 1, PRSS1) gene have been identified as causing HP. The R122H (previously known as R117H) mutation is the commonest and can be detected by a single and rapid polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) based technique using the AflIII enzyme. This test however may give a false negative result in the presence of a neutral polymorphism within the enzyme recognition site. The frequency of this event was examined by sequencing studies in patients with HP and in healthy controls. METHODS: Of 60 families identified by the UK and Ireland consortium of EUROPAC (European Registry for Hereditary Pancreatitis and Familial Pancreatic Cancer), 51 were screened for R122H, N29I, and A16V mutations using standard techniques, and by sequencing of all five exons of cationic trypsinogen. RESULTS: Twelve families had the N29I mutation, one family had A16V and, on standard testing, 15 families had the R122H mutation. An additional family with the R122H mutation was found on direct sequencing. The false negative result was due to a neutral polymorphism C-->T at the third base of the codon, not affecting the amino acid coded for, destroying the AflIII restriction site. This polymorphism was not observed in 50 DNA specimens (100 chromosomes) from controls nor from 50 individuals from PRSS1 mutation negative HP families. A novel mutation specific PCR was developed to avoid this pitfall. CONCLUSIONS: One of the 16 families with HP and an R122H mutation contained a polymorphism affecting the AflIII restriction site. Adoption of an alternative R122H assay is important for genetic studies in individuals with apparent HP.

Acute Disease↗
PubMed2000

Cystic fibrosis in infertility: screening before assisted reproduction: opinion.

Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. In 97-98% of men with CF, bilateral congenital absence of the vas deferens (CBAVD) blocks the transport of spermatozoa resulting in azoospermia. Abnormalities in sperm parameters have also been identified in males with CF. To date, over 800 disease-causing mutations of the CF transmembrane conductance regulator (CFTR) gene have been identified (also called ABCC7). Current legislation suggests that prior to intracytoplasmic sperm injection (ICSI) treatment, men with CBAVD or unexplained oligozoospermia should be considered for screening. If the male is negative with routine screening then the female partner is not screened. This is fundamentally wrong because if the female is screened and is found to be CF positive on routine testing, her partner would then need the fullest possible investigation of the CFTR gene. It is ideal to screen both partners in cases of oligozoospermia. However, if the resources are stretched, then only the female needs to be routinely screened because if she is negative, then the couple's residual risk of having a CF or CBAVD child will be reduced to 1:960. Only when the female is found to be a carrier does the male partner need routine screening followed by full testing for known mutations.

Cystic Fibrosis↗
PubMed1999

Small bowel bacterial overgrowth in subjects living in residential care homes.

OBJECTIVES: in elderly people, bacterial overgrowth of the small bowel may be occult. The significance of positive breath tests are uncertain: many fit elderly subjects with positive tests show no evidence of malabsorption. We assessed the prevalence and significance of bacterial overgrowth in the small bowel in a relatively unselected elderly population. METHODS: residents of seven elderly people's homes had a glucose hydrogen breath test. A medical history and anthropomorphic measurements were recorded. Volunteers with positive breath tests were given doxycycline. After 4 months all volunteers were reassessed. RESULTS: of 140 residents, 62 were tested. Nine (14.5%) had a positive breath test. There was no difference in anthropomorphic and bowel habit data between those with positive and those with negative breath tests. After 4 months of antibiotic treatment, volunteers with a positive breath test had increased weight and body mass index, while those with a negative test had decreased weight and body mass index. CONCLUSIONS: the percentage of volunteers with a positive breath test was much lower than in previous studies. This may be due to the relatively unselected nature of the volunteers. Treatment of bacterial overgrowth resulted in a small but significant improvement in anthropometric indices. The lack of association of positive breath tests with baseline anthropomorphic measurements or bowel habit highlights the occult nature of the bacterial overgrowth and questions its clinical importance.

Aged↗
PubMed1998

Molecular diagnosis of spinal muscular atrophy.

The frequency of deletions within the survival motor neurone (SMN) and neuronal apoptosis inhibitory protein (NAIP) genes in patients with spinal muscular atrophy (SMA), and the impact of this on the diagnosis and prenatal diagnosis of SMA, were investigated by molecular analysis of stored DNA and retrospective review of case notes. In type I SMA, 16 of 17 cases were homozygously deleted for exons 7 and 8 of SMN, 14 of 17 were homozygously deleted for exon 5 of NAIP, and 13 of 17 were deleted for both. In types II and III SMA, seven of nine cases were deleted for exons 7 and 8 of SMN. Deletions of SMN and NAIP occurred in four of nine cases. With one exception, the deletion genotypes of probands, affected siblings, and terminated fetuses were identical. Molecular studies are replacing conventional investigations for SMA and have a high uptake prenatally.

Cyclic AMP Response Element-Binding Protein↗
PubMed1997

Missense mutation clustering in the survival motor neuron gene: a role for a conserved tyrosine and glycine rich region of the protein in RNA metabolism?

The Survival Motor Neuron (SMN) gene shows deletions in the majority of patients with Spinal Muscular Atrophy (SMA), a disease of motor neuron degeneration. To date only two missense mutations have been reported in SMN in patients with SMA. The fact that no SMN-homologues have been forthcoming from data-base searching has resulted in a lack of hypotheses concerning the structural and functional consequences of these mutations. Recently SMN has been shown to interact with heterogeneous nuclear ribonucleoproteins (hnRNPs) suggesting a role in mRNA metabolism. We describe a novel missense mutation and the subsequent identification of a triplicated tyrosine-glycine (Y-G) peptide sequence at the C-terminal of SMN which encompasses each of the three predicted amino acid sequence substitutions. We have identified apparent orthologues of SMN in Caenorhabditis elegans and Schizosaccharomyces pombe. These sequences retain the highly conserved Y-G motif and provide additional support for a role of SMN in mRNA metabolism.

Amino Acid Sequence↗
PubMed1997

Hereditary pancreatitis and familial pancreatic cancer.

Important advances in the understanding of pancreatic diseases have taken place through the application of molecular methods in the study of the inherited form of pancreatitis and pancreas cancer. Mutations of the cationic trypsinogen gene have been found to be causative for hereditary pancreatitis with important implications for the molecular pathogenesis of acute and chronic pancreatitis. A variety of cancer syndromes involving the P16 and BRCA2 genes, for example, also lead to pancreatic cancer, but the gene responsible for familial pancreatic cancer has not been identified so far. The establishment of a European Registry of Hereditary Pancreatitis and Pancreatic Cancer (EUROPAC) will facilitate future developments.

Family Health↗
PubMed1993

New markers for linkage analysis of X-linked hypophosphataemic rickets.

Three polymorphic markers have been used to improve the genetic map of the region Xp22.1-p22.2, which contains the HYP (hypophosphataemic rickets) locus. DXS365 gave no recombinants with HYP, with a peak Lod score of 5.4 at theta = 0.0. A microsatellite marker mPA274 was derived for the DXS274 locus; it detects five alleles with a polymorphism information content of 0.55. Combining information from this microsatellite and the original DXS274 marker, probe CRI-L1391, the peak Lod score for DXS274 against HYP was 9.6 at theta = 0.02. A microsatellite associated with the DXS207 locus (mPA207) gave a peak lod score against HYP of 4.7 at theta = 0.14. A consideration of key recombinants and multilocus analysis suggests the gene order. Xpter-DXS207-DXS43-DXS197-(DXS365,HYP)- DXS274-DXS41-Xcen.

Base Sequence↗
PubMed1993

Occurrence of Duchenne dystrophy in Klinefelter's syndrome.

A boy with Duchenne muscular dystrophy and facial dysmorphism in conjunction with Klinefelter's genotype 47XXY is presented; this is an unusual situation with two genetic errors evolving over two generations. Karyotyping should be considered in boys with Duchenne muscular dystrophy who have unusual features.

Child, Preschool↗
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↗
PubMed1989

Molecular genetics in the National Health Service in Britain.

A recent report from the Departments of Health draws attention to the value of DNA diagnosis for inherited diseases and the need for planning these services in the National Health Service. There is great potential for preventive medicine, but a major immediate benefit is the newfound ability to exclude the carrier state in many people at risk and to protect fetuses from abortion when, as in most cases, they are shown to be normal by DNA tests. However, the widespread application of these new techniques requires prior evaluation and general acceptance. This will only be obtained after public debate, education of professionals and the population, and the establishment of adequate non-directive genetic counselling services. Some of the points to be considered in setting up molecular genetics laboratories are described.

Cystic Fibrosis↗
PubMed1988

Common organization of gene clusters for production of different capsular polysaccharides (K antigens) in Escherichia coli.

Southern blot analysis of cloned K5- and K7-antigen genes, using DNA fragments from cloned K1 genes as radiolabeled probes, demonstrated that each K-antigen gene cluster is organized in a manner similar to that shown for the K1 antigen. That is, a central DNA segment unique for a given antigen type is flanked by DNA sequences that encode common functions for the management of intracellular polymer. This has been confirmed by transposon and deletion mutagenesis of plasmids carrying the K5 and K7 genes. We also describe a series of complementation experiments in which transport or postpolymerizational modification functions for one K antigen are used to complement mutations in the corresponding regions of a different K-antigen gene cluster. Thus, postpolymerizational modification of polysaccharide and transport of mature polysaccharide from the periplasmic space are common mechanisms and are independent of polysaccharide structure.

Antigens, Bacterial↗