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S M Huson

Publications and source records attributed to S M Huson.

At least 73 records · Page 4Linked to original sources
PubMed1989

A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity.

A population based study of von Recklinghausen neurofibromatosis in south east Wales (population 668,100) identified 69 families with 135 affected members (prevalence 1/4950 of the population). In these families penetrance of the NF-1 gene was 100% by the age of five years. The genetic fitness of NF-1 sufferers was found to be reduced to 0.47, the effect being more marked in males than females (f = 0.31 and 0.60, respectively). Forty-one of 135 cases were judged to represent new disease mutations and the mutation rate was estimated to lie between 3.1 x 10(-5) and 10.4 x 10(-5). A parental age effect for new mutations was not found, nor was a maternal effect on disease severity.

Adolescent↗
PubMed1989

A genetic study of von Recklinghausen neurofibromatosis in south east Wales. II. Guidelines for genetic counselling.

The age of appearance and diagnostic value of the major defining features of von Recklinghausen neurofibromatosis (NF-1) have been studied in 168 cases from 73 families. In assessing children of an affected patient, those who have inherited the gene can be distinguished from their normal sibs on the basis of whether or not café au lait (CAL) spots are present by the age of five years. Lisch nodules appear before cutaneous neurofibromas and are a useful clinical aid in the assessment of unusual cases, those in whom the diagnosis is equivocal, and children with multiple CAL spots but no family history of NF-1. Sixty-nine of the families were identified through a population based study in south east Wales and the frequency of complications in 135 affected subjects from these families has been used to develop figures for genetic counselling. For these purposes, the complications of NF-1 can be usefully divided into four categories: intellectual handicap (33%) (moderate/severe retardation 3.2%, minimal retardation/learning difficulties 29.8%); complications developing in childhood and causing lifelong morbidity (8.5%); 'treatable' complications which can develop at any age (15.7%); and malignant or CNS tumours (4.4 to 5.2%).

Adolescent↗
PubMed1989

Close flanking markers for neurofibromatosis type I (NF1).

A genetic linkage study with 16 polymorphic DNA markers spanning the region 17p11-17q24 in 22 NF1 families is presented. Close linkage between NF1 and eight pericentromeric markers (HHH202, EW206, CRI-L946, EW203, EW301, FG2, p17H8, and CRI-L581) has been found, probe HHH202 being the closest marker to NF1. Genetic heterogeneity has been excluded. The study of multiply informative meioses suggests that the probes HHH202 and RW206 are flanking markers for NF1. The most likely order on the basis of multiply informative meioses and multipoint mapping is pter-pA10.41-EW301-cen-HHH202-NF1-EW206-++ +EW207-qter.

Chromosome Mapping↗
PubMed1988

Greig cephalopolysyndactyly syndrome: a possible mouse homologue (Xt-extra toes).

Greig cephalopolysyndactyly syndrome is an autosomal dominant form of complex polydactyly in man. Attention is called to the evidence that, on both morphological and comparative gene mapping grounds, this defect is homologous to Xt-extra toes in the mouse. The pattern of polydactyly in both species is very similar. In addition, both conditions probably map close to the T-cell receptor gamma polypeptide at 13 A2-3 in mouse and 7p15 in humans.

Animals↗
PubMed1988

Chromosomal localisation of a developmental gene in man: direct DNA analysis demonstrates that Greig cephalopolysyndactyly maps to 7p13.

Greig cephalopolysyndactyly syndrome (GCPS) is a rare autosomal dominant form of complex polydactyly. GCPS has been tentatively assigned to chromosome 7 on the basis of association of the condition with balanced translocations involving the short arm of chromosome 7 (7p13) in two families. Seven GCPS pedigrees with no chromosome abnormality were studied, and linkage was demonstrated between GCPS and the DNA sequence coding for the receptor for epidermal growth factor (localised to 7p12-13) (Z = 3.17; O = theta).

Chromosomes, Human, Pair 7↗
PubMed1988

Von Recklinghausen neurofibromatosis. A clinical and population study in south-east Wales.

A population-based study in south-east Wales (population 668,100) identified 135 patients with von Recklinghausen neurofibromatosis (prevalence 20/10(5]. In addition to multiple café-au-lait spots and/or dermal neurofibromas, freckling was present in the axilla (67%), groin (44%) or submammary areas (29% of adult females). Although not a criterion for diagnosis, Lisch nodules were almost invariably present in the iris (93% of patients overall; 96% of those aged greater than or equal to 20 yrs). The complications of von Recklinghausen neurofibromatosis in this cohort (n = 135 unless stated) were plexiform neurofibromas (40/125), severe mental retardation (1), epilepsy (6), optic glioma (2), spinal neurofibroma (2), aqueduct stenosis (2), meningioangiomatosis (1), scoliosis requiring surgery (6), pseudoarthrosis (3), delayed puberty (2), visceral and endocrine tumours (6), and congenital glaucoma (1). There were no cases of acoustic neuroma. Considering all living family members aged greater than or equal to 18 yrs, together with their deceased relatives, the frequency of CNS and malignant tumours related to the disease was 4.4-5.2%. Uncomplicated von Recklinghausen neurofibromatosis is disfiguring but not a major cause of morbidity. The management of the disease relates to its complications which can be divided into three categories: those which occur in childhood and cause lifelong morbidity (moderate-severe mental handicap, facial plexiform neurofibromas, orthopaedic), those which can occur at any time but are 'treatable' (benign disorders of the nervous system, visceral and endocrine tumours, renal artery stenosis), and malignant or CNS tumours. The combined frequency for each category based on this survey was 12%, 16% and 4.4-5.2%, respectively.

Adolescent↗
PubMed1987

Chromosome 17 markers and von Recklinghausen neurofibromatosis: a genetic linkage study in a British population.

A genetic linkage study of the RFLPs identified by nine DNA probes localized to the pericentromeric region and long arm of chromosome 17 has been undertaken in 16 families with von Recklinghausen neurofibromatosis (NF1). Close linkage has been shown with the markers CRI-L946 (D17S36), CRI-L581 (D17S37), p17H8 (D17Z1), and pA10-41 (D17S71). The ERBA1 and COL1A1 loci may also be closely linked, but the data are limited. The results for HOX2 and NGFR suggest only loose linkage with the NF1 gene, while no linkage was found between NF1 and the growth hormone locus. No suggestion of nonallelic heterogeneity of NF1 was found in this study.

Chromosomes, Human, Pair 17↗
PubMed1987

An exclusion map for Von Recklinghausen neurofibromatosis.

By using all the genetic linkage data available between Von Recklinghausen neurofibromatosis (VRNF) and various loci on the autosomes, a graphical display of all the non-excluded areas is presented. The probability of VRNF being on any of the 22 autosomes is also shown. The exclusion map presented is for 90 markers that have been localised relatively accurately. Data are also presented for a further 24 markers that have not yet been adequately localised. This exclusion map shows that most of the genome has been excluded as a likely location of any locus responsible for this disorder in the majority of families. Chromosomes 5, 10, 17, and 18 remain largely unexcluded. Concentration on these parts of the genome should help in the identification of the site of the VRNF gene.

Chromosome Mapping↗
PubMed1986

Application of a closely linked polymorphism of restriction fragment length to counselling and prenatal testing in families with myotonic dystrophy.

The close genetic linkage between the loci for apolipoprotein CII (ApoC2) and myotonic dystrophy makes ApoC2 the closest fully validated marker for prediction of myotonic dystrophy. Application to genetic counselling and presymptomatic and prenatal prediction is reported in seven families with myotonic dystrophy, including one case in which the disorder was excluded prenatally. Only one of the families did not have members with ApoC2 genotypes that allowed prediction, but careful clinical study of older family members was found to be an important factor. ApoC2 typing of families with myotonic dystrophy should be of practical help both in prediction for asymptomatic relatives and for prenatal diagnosis in pregnancies of an affected parent.

Adult↗
PubMed1986

Regional localisations and linkage relationships of seven RFLPs and myotonic dystrophy on chromosome 19.

We have studied the genetic linkage relationships of seven DNA polymorphisms on chromosome 19, with each other and with the myotonic dystrophy locus. The DNA sequences were localised to various regions of the chromosome using translocations in somatic cell hybrids. These results provide the basis for a linkage map of most of chromosome 19, and suggest that the myotonic dystrophy locus is close to the centromere.

Animals↗
PubMed1986

Linkage relationships of the insulin receptor gene with the complement component 3, LDL receptor, apolipoprotein C2 and myotonic dystrophy loci on chromosome 19.

Myotonic dystrophy is associated with disturbances in the insulin response, possibly due to an abnormality of the insulin receptor. Both the myotonic dystrophy (DM) and insulin receptor (INSR) genes are on chromosome 19. Using a cloned gene probe for INSR, we have studied its linkage relationships with the DM locus and other chromosome 19 markers. The results show that INSR is not closely linked to DM, but is located very close to C3, in the region 19pter-19p13.2. This implies that the basic genetic defect which causes DM is not directly responsible for the disturbed insulin response in these patients.

Apolipoprotein C-II↗
PubMed1986

Cerebellar haemangioblastoma and von Hippel-Lindau disease.

Von Hippel-Lindau disease is an autosomal dominant multisystem disorder, the commonest presenting manifestations of which are haemangioblastomas of the cerebellum and retina. Affected individuals are at risk of developing a number of other lesions, the most serious of which are renal carcinoma, haemangioblastomas elsewhere in the central nervous system and phaeochromocytoma. Patients with this disease can therefore present to a number of disciplines during their lifetime and unless the possibility of von Hippel-Lindau disease is considered, the patient may wrongly be assumed to have an isolated lesion. Twenty patients with cerebellar haemangioblastomas were seen between 1972 and 1985; the diagnosis of von Hippel-Lindau disease was subsequently established in 8. Although the diagnosis had not previously been considered, in retrospect 7/8 cases were known to be at risk of this syndrome. These cases came from 7 families and an additional 4 relatives are also known to have been affected. Mean age of presentation for the various manifestations of von Hippel-Lindau disease, each of which occurred in one or other of our cases, has been calculated from 9 of our patients and 107 others reported in the literature. Clinically significant manifestations almost invariably developed before the age of 50 years. Limited screening of our index cases and their at-risk relatives demonstrated one asymptomatic renal carcinoma. We propose a protocol for screening all individuals at risk of von Hippel-Lindau disease, which involves annual retinal examination from five years, and biennial computerized tomography of the head and abdomen from fifteen and twenty years, respectively.

Adolescent↗
PubMed1986

Linkage analysis of peripheral neurofibromatosis (Von Recklinghausen disease) and chromosome 19 markers linked to myotonic dystrophy.

Three chromosome 19 markers known to be linked to myotonic dystrophy have been studied in nine families with peripheral neurofibromatosis (Von Recklinghausen's disease). Clear evidence against linkage has been found for all three markers, excluding the peripheral neurofibromatosis gene from the myotonic dystrophy region of chromosome 19. Previous reports of co-inheritance of the two disorders in families cannot therefore be explained on the basis of close genetic linkage between the loci.

Adult↗