Biomedical subjects
Publications and source records attributed to J Burn.
To enquire whether the known X linked probes linked to the Duchenne muscular dystrophy gene vary in their RFLP frequencies, three probes, 754, XJ1.1, and pERT87.8, were tested in European, Indian Muslim, and West African samples. Though the average heterozygosity for the three together is fairly similar in the three populations, significant differences in allele frequencies were evident.
A 27-year-old male with hypomelanosis of Ito (HI) is reported. One of his two children had a postaxial ray defect of one leg but neither had cutaneous features of HI. Somatic mosaicism for a gene defect lethal to ectodermal derivatives offers the best explanation for HI in males, with consequent negligible recurrence risk. The limb defect is considered coincidental. The excess of girls with HI could be due to a female cohort with incontinentia pigmenti (IP) which may be indistinguishable: counselling of females must therefore take account of possible X-linked inheritance.
Supravalvular aortic stenosis (SVAS) may occur as an isolated autosomal dominant trait or as a feature of Williams syndrome. It has been suggested that a defect in calcitonin function may play a role in Williams syndrome. We have excluded calcitonin as a candidate gene for SVAS using a gene specific probe.
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The linkage of rheumatoid arthritis (RA) to the HLA-DR locus was investigated in 17 families with multiple cases of RA. Log odds scores were computed using the Liped program; sibship associations were examined by 2 methods. The results showed a trend toward linkage which was short of significance. The results were similar for patients with classic or definite RA, with or without the inclusion of probable RA patients. The finding of strong association and weak linkage would suggest that it is DR4, itself, that is important in RA.
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Three cases of twins conjoined across the chest were examined. In one set, one twin showed right atrial isomerism and the other showed the usual atrial arrangement. The other two sets showed the usual atrial arrangement in both twins. The associated cardiac anomalies were diverse, ranging from atrioventricular septal defects to absent atrioventricular connections. Sequential segmental analysis was used successfully in each case to classify the complex cardiac anomalies. The first step was the recognition of the atrial arrangement. This was easily achieved despite the complexity of the intracardiac morphology.
Four infants who were exposed to sodium valproate or valproic acid during pregnancy are described. Common facial features in the three surviving infants include epicanthic folds, a flat nasal bridge, a broad nasal base, anteverted nostrils, a shallow philtrum, and a thin upper lip with a thick lower lip. Ridging of the metopic suture, congenital heart defect, postaxial polydactyly, and hypospadias were additional features in individual cases. In agreement with previous authors, we feel that there is a distinctive 'fetal valproate' phenotype.
We report a girl aged 11 and her brother aged five, both with the typical features of Angelman syndrome, and three isolated cases. This report, together with a review of published reports and contact with previous authors, has revealed a total of 41 sibs of probands, although only nine of these are known to have been later born. The possible effect of voluntary restriction of family size after the birth of an affected child is discussed in relation to the possibility of autosomal recessive inheritance, but a recurrence risk of 5% is appropriate for use in the genetic clinic.
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Most individuals with cat eye syndrome (CES) have a supernumerary bisatellited chromosome which, on the basis of cytogenetic evidence, has been reported to originate from either chromosome 13 or 22. To resolve this question, a single-copy DNA probe, D22S9, was isolated and localized to 22q11 by in situ hybridization to metaphase chromosomes. The number of copies of this sequence was determined in CES patients by means of Southern blots and densitometry analysis of autoradiographs. In patients with the supernumerary chromosome, four copies were found, whereas in one patient with a duplication of part of chromosome 22, there were three copies. Therefore, the syndrome results from the presence of either three or four copies of DNA sequences from 22q11; there is no evidence that sequences from other chromosomes are involved. This work demonstrates how DNA sequence dosage analysis can be used to study genetic disorders that are not readily amenable to standard cytogenetic analysis.
Recombination of an inherited pericentric inversion of chromosome 20 has given rise to a child with partial trisomy 20p. To our knowledge no previous familial inversions of this chromosome have been described in the literature.
We report two children, the products of a consanguineous union, who died in infancy. Both children had severe microcephaly intracranial calcification, lissencephaly and polymicrogyria.
Warburg syndrome is a recently defined autosomal recessive oculocerebral syndrome. It was previously given the acronym HARD +/- E, indicating what were regarded as the pathognomonic features, namely hydrocephalus, agyria, and retinal dysplasia with or without encephalocele. We report the case of a male infant with the typical cerebral features of hydrocephalus, agyria, and pseudoencephalocele, but without retinal dysplasia. Peters' anomaly and optic nerve hypoplasia were the main ocular defects. We believe that anterior chamber defects and optic nerve hypoplasia are the ocular defects more directly related developmentally to the cerebral defects. Definition of ocular defects is important, since diagnosis and counselling rely heavily on ocular signs, which help to distinguish this syndrome from neural tube defects in general.
A family is presented in which at least five members in three generations suffered a characteristic syndrome of generalised lipoatrophy, sparing the head and neck, and muscle hypertrophy variably associated with high plasma insulin and lipid levels and insulin resistant diabetes. This pedigree contains the first documented affected male with the syndrome. The diagnosis is of practical importance since close medical supervision of asymptomatic gene carriers is likely to improve their prognosis. The findings in this family have relevance also to the study of insulin and lipid metabolism.
We review a family in which a mother and two of her three children suffered a distinct syndrome of thoracic dystrophy with small chest volume, laryngeal stenosis, normal stature with variable asymmetry, asthenic build, and a small pelvis. In addition to the different inheritance pattern, this syndrome is distinguished from the better known Jeune syndrome by the differing thoracic and pelvic configuration.