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Biomedical subjects

S Bundey

Publications and source records attributed to S Bundey.

At least 37 records · Page 2Linked to original sources
PubMed1994

X inactivation patterns in female monozygotic twins and their families.

X inactivation studies have been carried out on 22 pairs of female monozygotic twins, one set of female monozygotic triplets, and their mothers and singleton sisters, using the probe M27 beta. Forty-eight per cent of the twins, 55% of their mothers, and 42% of their singleton sisters showed skewed X inactivation. Two of the triplets and their mother had random X inactivation, while the third triplet showed skewed X inactivation. Their singleton sister was homozygous with M27 beta. Of the twins, six pairs showed skewed X inactivation in favour of the same X chromosome, one pair showed skewed X inactivation favouring opposite X chromosomes, in seven pairs one twin showed skewed X inactivation while her co-twin showed random X inactivation, and in eight pairs both twins were random. A higher frequency of skewed pattern of X inactivation was not observed in the monozygotic twins when compared to a series of non-twin females (mothers and singleton sisters) and, so, the results in this study do not lend support to the theory that skewed X inactivation predisposes to the twinning process.

Adult↗
PubMed1994

Retinitis pigmentosa families showing apparent X linked inheritance but unlinked to the RP2 or RP3 loci.

Three families with retinitis pigmentosa (RP) are described in which the disorder shows apparent X linked inheritance but does not show linkage to the RP2 and RP3 regions of the short arm of the X chromosome. The families are also inconsistent with a localisation of the disease gene between DXS164 and DXS28. In one case, reassessment of the family in the light of these results suggested that the family may have an autosomal dominant form of RP. The remaining two families are consistent with X linkage and suggest the possibility of a new X linked RP (XLRP) locus. These families highlight the difficulties in determining the mode of inheritance on the basis of pedigree structure and clinical data alone. Molecular genetics plays an important role in confirming the mode of inheritance and in detecting potential misclassifications, particularly in a group of disorders as heterogeneous as RP. They emphasise that caution is required in genetic counselling of RP families, particularly in the absence of any molecular genetic analysis.

Adult↗
PubMed1994

Clinical and genetic features of ataxia-telangiectasia.

There are several variants of ataxia-telangiectasia (A-T): classical A-T with marked radiation sensitivity; classical A-T with intermediate levels of radiation sensitivity; mild A-T with intermediate levels of radiation sensitivity; A-T without telangiectasia; A-T without oculomotor apraxia; and A-T with microcephaly. These disorders are probably caused by different allelic mutations, because affected sibs resemble the index patients, and because there is an association of certain haplotypes of 11q22-23 with specific phenotypes. The Nijmegen Breakage Syndrome, with its lack of ataxia, seems on clinical grounds to be a different disorder. Although A-T is almost always inherited as an autosomal recessive, there are some unusual features; an unexpectedly low parental consanguinity rate, an incidence in sibs that is < 0.25, and occurrence of disease in many different races and in the offspring of mixed race unions. Moreover, looking at haplotypes from 63 UK patients, there is a remarkably low incidence of homozygosity. An autosomal recessive condition that is deficient in parental consanguinity, and in homozygosity for the region around the gene, can be explained by J. H. Edwards' hypothesis that homozygosity for alleles at a neighbouring locus are lethal early in embryogenesis. Other possible mechanisms to explain the unusual genetic features are discussed.

Adolescent↗
PubMed1993

A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by an abnormality of the peripheral retina. Both autosomal dominant (adFEVR) and X-linked (XLFEVR) forms have been described, but the biochemical defect(s) underlying the symptoms are unknown. Molecular analysis of the Norrie gene locus (NDP) in a four generation FEVR family (shown previously to exhibit linkage to the X-chromosome markers DXS228 and MAOA (Xp11.4-p11.3)) reveals a missense mutation in the highly conserved region of the NDP gene, which caused a neutral amino acid substitution (Leu124Phe), was detected in all of the affected males, but not in the unaffected family members, nor in normal controls. The observations suggest that phenotypes of both XLFEVR and Norrie disease can result from mutations in the same gene.

Adolescent↗
PubMed1993

X linked exudative vitreoretinopathy: clinical features and genetic linkage analysis.

A four generation family in which familial exudative vitreoretinopathy is inherited as an X linked condition is described. Essentially the condition is one of abnormal vascularisation and signs at birth are those of a retinopathy superficially resembling retinopathy of prematurity, retinal folds, or, in advanced cases, enophthalmos or even phthisis. Prognosis depends on the progression of the retinal changes. The family members, including seven affected males and five obligate carrier females, have been types for 20 DNA markers, and linkage analysis suggests a gene locus either at Xq21.3 or at Xp11. As the latter region includes the locus for the gene for Norrie disease, it is possible that this and X linked vitreoretinopathy are allelic. We can further speculate that the differences in severity of the clinical manifestations are dependent only upon the timing of the insult.

Adolescent↗
PubMed1993

A five-year prospective study of the health of children in different ethnic groups, with particular reference to the effect of inbreeding.

A 5-year prospective study of 4,934 children of different ethnic groups has demonstrated a 3-fold increase of postneonatal mortality and childhood morbidity in the offspring of consanguineous Pakistani parents. Most of these families contained more than one consanguineous union, resulting in a mean inbreeding coefficient for their children of 0.0686. It is estimated that 60% of the mortality and severe morbidity of this group of children could be eliminated if inbreeding ceased. However consanguinity is much favoured in this minority group, and health education will have to be carefully and sensitively handled.

Bangladesh↗
PubMed1993

Mutations of the tyrosinase gene in Indo-Pakistani patients with type I (tyrosinase-deficient) oculocutaneous albinism (OCA).

Oculocutaneous albinism (OCA) is a group of autosomal recessive disorders characterized by deficient synthesis of melanin pigment. Type I (tyrosinase-deficient) OCA results from mutations of the tyrosinase gene (TYR gene) encoding tyrosinase, the enzyme that catalyzes the first two steps of melanin biosynthesis. Mutations of the TYR gene have been identified in a large number of patients, most of Caucasian ethnic origin, with various forms of type I OCA. Here, we present an analysis of the TYR gene in eight Indo-Pakistani patients with type I OCA. We describe four novel TYR gene mutations and a fifth mutation previously observed in a Caucasian patient.

Adolescent↗
PubMed1993

Mitochondrial myopathy associated with sudden death in young adults and a novel mutation in the mitochondrial DNA leucine transfer RNA(UUR) gene.

A family exhibited maternal inheritance of a variable syndrome comprising ocular, neck and proximal upper limb weakness, psychiatric features, and sudden death. Of 15 definitely or probably affected individuals, 7 had died in early adult life, probably of respiratory failure. A novel point mutation of mitochondrial DNA, in a transfer RNA gene at position 3251, was detected in all living affected family members.

Adult↗
PubMed1992

Multiple mutation in an extended Duchenne muscular dystrophy family.

We have investigated an extended pedigree with three cousins affected by Duchenne muscular dystrophy with apparent transmission through the male line. However, molecular studies have shown that one boy has a de novo duplication, another has a deletion, and the molecular mutation has yet to be defined in the third boy. All three X chromosomes in the affected boys appear to have a different origin. We speculate on the mechanisms by which the Duchenne locus may be particularly prone to mutation in this family and the possible involvement of transposons is discussed. Whatever the mechanism involved, the occurrence of three different mutations in one pedigree is a rare event.

Adolescent↗
PubMed1992

Racial distribution of Duchenne muscular dystrophy in the West Midlands region of Britain.

In the West Midlands region of Britain, Duchenne muscular dystrophy (DMD) is twice as common as expected in Indians, and is less common than expected in Pakistanis. Although the numbers are small, they cannot be explained by any bias of ascertainment and are considered to be real. One possible mechanism for the high frequency of DMD in Indians is the presence of repetitive elements in the wild type gene which predispose to mutations.

Africa, Eastern↗
PubMed1991

Uses and limitations of twin studies.

Series of twin pairs selected because one (or both) is ill are prone to biassed ascertainment, and great care has to be taken to avoid this. Such bias is absent if the primary source is a twin registry established at birth. In general, series of twin pairs have no advantage over studies on sibs in assessing the size of genetic contribution to disease. However, individual monozygotic twin pairs who are discordant for single gene or multifactorial conditions offer unique opportunities for investigating postzygotic mutations, for searching for factors that may precipitate disease or influence its course, and for assessing the effect of prophylactic measures.

Humans↗
PubMed1991

A family with three sisters with the 4p- syndrome, originally reported as suffering from the Smith-Lemli-Opitz syndrome.

The authors further describe investigations of a family originally reported by Bundey & Smyth in 1974 with a diagnosis of the Smith-Lemli-Opitz syndrome. Chromosome studies performed for the fourth time revealed that the mother had a presumptive t(4;22) translocation. The importance of reviewing earlier diagnoses, including repeating the chromosome studies if indicated, in order to arrive at a more accurate diagnosis is stressed. It is also important to provide the cytogenetics laboratory with clues to any possible clinically-recognisable chromosome syndrome, and to be prepared to examine the chromosomes of the parents of the affected case, even if the patient's karyotype appears normal. In this particular family, the correct diagnosis in the affected girls led to a realization that their brother had a 50% risk of producing unbalanced offspring.

Adolescent↗
PubMed1991

Why do UK-born Pakistani babies have high perinatal and neonatal mortality rates?

A prospective study of 4934 babies of different ethnic groups has confirmed the high perinatal mortality rate for Pakistanis and has shown that this was not due to a reluctance to terminate a fetus who is known to be seriously malformed. The major cause of early mortality was a high rate of lethal malformations, which occurred in about 1 in 100 Pakistani babies and which accounted for about half of their perinatal mortality. Many of these were autosomal recessive and occurred only in the offspring of consanguineous parents. However, there was also an excess of lethal cardiac malformations which were not associated with parental consanguinity. The remainder of the excess perinatal mortality was probably due to socio-economic factors. These causes are partly amenable to preventive measures, such as the referral of Pakistani women for expert ultrasonography at 18 to 20 weeks of pregnancy.

Cause of Death↗