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Biomedical subjects

J M Connor

Publications and source records attributed to J M Connor.

At least 127 records · Page 7Linked to original sources
PubMed1989

Molecular genetics of Turner's syndrome.

Recombinant DNA technology now allows an analysis of sex chromosomal abnormalities at the molecular level. X chromosomes differ in respect of their pattern of cutting sites for particular restriction enzymes; these differences can be used to determine which X chromosomes or which part of an X chromosome has been inherited from a parent. Furthermore, these techniques can be used to define the presence or absence of particular regions of the X chromosomes with a higher level of resolution than it is possible to achieve using light microscopy. Thirty-eight families in which there was a child or fetus with Turner's syndrome were studied using a series of DNA probes that detect differences (restriction fragment length polymorphisms) among X chromosomes. Analysis of the origin of the normal X chromosome was possible in 27 families. In 14 families with 45,X the observed X was maternal in each, whereas in 13 children with other karyotypes (46,X,i(Xq); 45,X/46,X,i(Xq); 45,X/46,XX; 45,X/46,X,r(X)) the origin of the normal X was paternal in six and maternal in seven patients. In two other families, mosaicism, which was unsuspected at chromosomal analysis, was revealed. DNA probes studied in the remaining nine families were uninformative. These results suggest that different pathogenic mechanisms operate for pure 45,X when compared with the other karyotypes associated with Turner's syndrome. The presence of unsuspected mosaicism in some of these families has clinical implications in relation to prognosis and management.

Female↗
PubMed1989

Genetic aspects of tuberous sclerosis in the west of Scotland.

Complete ascertainment of tuberous sclerosis was attempted in the west of Scotland (population 2,763,000). A total of 101 patients was identified, giving an overall minimum prevalence of 1 in 27,000, but for children under 10 years of age the minimum prevalence was 1 in 12,000. Both parents of 84 of the ascertained cases were assessed for signs of tuberous sclerosis. In 51 pairs of parents no evidence of the condition was seen, indicating that up to 60% of the cases were new mutations. The mutation rate was estimated at 2.5 X 10(-5) mutations per gene per generation. Analysis of parental ages for the new mutations did not show a significant age effect. Thirty-five patients occurred in 13 families containing other affected subjects. The pattern of inheritance was consistent with an autosomal dominant trait in these families. In one sibship, non-penetrance or gonadal mosaicism resulted in affected sibs with normal parents. Of two further sibships where non-penetrance was suspected, one was shown to represent a single new mutation in monozygotic twins and the other to involve non-paternity.

Adult↗
PubMed1989

Dominant inheritance of Scheuermann's juvenile kyphosis.

We report a family in which Scheuermann's juvenile kyphosis is present in three successive generations with male to male transmission. This provides further evidence for autosomal dominant inheritance in at least some families with this condition.

Adolescent↗
PubMed1989

Evidence for genetic heterogeneity in tuberous sclerosis.

The question of genetic heterogeneity in tuberous sclerosis (TSC) was addressed by genetic linkage studies in eight affected families using nine polymorphic markers (EFD126.3, MCT136, ABO, ABL, AK1, and MCOA12 from distal 9q, and PBGD, MCT128.1, and 1CJ52.208M from distal 11q). The data as a whole supported a TSC locus on distal 9q, the peak lod score on multipoint analysis being 3.77 at 6 cM proximal to the Abelson oncogene locus (ABL). However, analysis of two point lod scores using the HOMOG programs showed significant evidence for genetic heterogeneity (p = 0.01), linkage to ABL being unlikely in one family. After exclusion of the unlinked family, multipoint analysis gave a peak lod score of 6.1 in the vicinity of ABL. The family unlinked to ABL showed no recombinants with two chromosome 11 probes, but was too small to provide significant evidence for linkage. Genetic heterogeneity in TSC will complicate efforts to clone the causative genes and severely limit the use of linked probes for carrier detection and prenatal diagnosis.

Chromosome Mapping↗
PubMed1989

Haplotype distribution of the human phenylalanine hydroxylase locus in Scotland and Switzerland.

RFLP haplotypes at the phenylalanine hydroxylase (PAH) locus were determined in 45 nuclear Caucasian families from Switzerland and Scotland. The RFLPs at the PAH locus are highly informative, and prenatal diagnosis is possible in 85% of the families studied. The data were combined with the profiles previously observed in the Danish population, in order to study the variation in RFLP haplotype distribution among European populations. A total of 22 different haplotypes were observed in Denmark, Switzerland, and Scotland. Fifteen and 19 haplotypes are associated with the normal (non-PKU) and with the mutant chromosomes, respectively. The haplotype distribution and the allele frequency of normal chromosomes remain constant between Denmark, Switzerland, and Scotland. However, both the haplotype distribution and allele frequencies of mutant chromosomes show significant variation between the three countries. Our results suggest there may be additional mutations in the PAH gene that cause PKU.

Alleles↗
PubMed1988

Genetic causes of mental handicap and opportunities for prevention.

Prior to 1970 nearly one half of severe mental handicap (IQ less than 50) was unexplained and genetic causes were recognized in one third of all patients. In recent years the genetic contribution has risen to 50%, with the decline in importance of environmental causes and the growing recognition of X-linked forms of mental retardation and chromosomal microdeletion syndromes. Recognition of genetic conditions is vital for accurate assessment of recurrence risks and in order, in some instances, to provide specific prenatal diagnosis. With full utilization of existing prenatal screening procedures and a more detailed family history, severe mental handicap due to genetic conditions should be reduced by 30-40%.

Brain↗
PubMed1988

Spondylothoracic and spondylocostal dysostosis. Hereditary forms of spinal deformity.

Two siblings with spondylothoracic dysostosis, and two siblings and three unrelated children with spondylocostal dysostosis are described. Both conditions are inherited and characterised by malformed thoracic and lumbar vertebrae. Spondylothoracic dysostosis produces "crab-like" deformities of the ribs, and is usually fatal during early infancy due to respiratory failure. Spondylocostal dysostosis causes short-trunked dwarfism but does not usually reduce life expectancy. These clinical features are distinct from congenital scoliosis, although all three conditions are associated with a particular group of malformations.

Abnormalities, Multiple↗
PubMed1987

Evidence that the gene for tuberous sclerosis is on chromosome 9.

Linkage analysis was undertaken in nineteen families with tuberous sclerosis by use of 26 polymorphic markers. All affected members fulfilled strict diagnostic criteria and unaffected members were rigorously investigated to confirm their status. Maximum lod scores were 1.20 for adenylate kinase 1 (AK1) at zero recombination and 3.85 for the ABO blood group at zero recombination (confidence limits 0-0.10). These findings support the assignment of the gene for tuberous sclerosis to the distal long arm of chromosome 9.

Adenylate Kinase↗
PubMed1987

Genetic aspects of early childhood scoliosis.

Eighty-seven families with early onset scoliosis were evaluated. These were divided into 3 groups: resolving infantile idiopathic scoliosis (15 families), progressive infantile idiopathic scoliosis (21 families), and congenital scoliosis due to vertebral malformations (51 families). The children with congenital scoliosis were subdivided into those who had closed neural arch defects (19 families) and those who did not (32 families). Resolving infantile idiopathic scoliosis was usually associated with plagiocephaly, and both deformations tended to show spontaneous recovery. These children were otherwise normal. Seven (33%) of the children with progressive infantile idiopathic scoliosis were mentally retarded, but only 2 had a congenital malformation. In contrast, 18 (33%) of the children with congenital scoliosis had other malformations, but only 2 were mentally retarded. The recurrence risk for scoliosis was low in each group studied. However, there was an increased risk (4% for sibs) of neural tube defects in the families with congenital scoliosis (with or without neural arch defects). This sib risk was apparent for probands with only a single hemivertebrum in addition to probands with more extensive vertebral defects and would support an etiological relationship between neural tube defects and other vertebral malformations.

Abnormalities, Multiple↗
PubMed1987

Microcephaly: genetic counselling and antenatal diagnosis after the birth of an affected child.

We describe the clinical and genetic details of a series of microcephalic patients who were referred to the Genetic Counselling Service for the West of Scotland. There were 29 isolated cases of microcephaly and 9 families with recurrent microcephaly. The sib recurrence risk was 19%, which reflects the high incidence of autosomal recessive microcephaly in this series. There was evidence for several varieties of recessive microcephaly. The most frequent, affecting 5 sib pairs, was associated with spastic quadriplegia, seizures, and profound mental handicap. In 15 families with one microcephalic child, prenatal diagnosis by serial ultrasound scans was undertaken in 21 subsequent pregnancies. Four recurrences of microcephaly were detected in the third trimester and one recurrence was missed because no scans were performed after 24 wk gestation when the ultrasound measurements indicated satisfactory head growth. The main reason for late diagnosis of affected fetuses was that head growth did not slow appreciably until the last trimester. The high recurrence risk in this prospective series emphasizes the contribution of autosomal recessive inheritance of microcephaly amongst patients of our Genetic Counselling Service.

Female↗
PubMed1987

Second trimester prenatal diagnosis of the Jarcho-Levin syndrome.

The Jarcho-Levin syndrome (spondylothoracic dysostosis) is a rare autosomal recessive disorder characterized by a short neck, short trunk and a constricted thorax due to multiple rib and vertebral defects; other visceral malformations are occasionally present. Most cases die in infancy due to respiratory failure. In this report we describe two cases in one family from the United Kingdom. Prenatal diagnosis by ultrasound examination during the second trimester was successfully accomplished in the second case.

Abnormalities, Multiple↗
PubMed1987

The ectopic kidney in the emergency department.

Renal ectopia can present as abdominal pain and be a predisposing factor to several pathologies seen in the genitourinary system. We present the case of a 21-year-old man with intermittent right lower quadrant abdominal pain who was found to have a nonfunctioning pelvic kidney and underwent nephrectomy. Although specific findings on renal ectopia are often absent, associated congenital defects above the pelvic organs raise the suspicion for renal ectopia. Early detection and recognition of the ectopic kidney can prevent long-term complications.

Adult↗
PubMed1987

Linkage analysis using multiple Xq DNA polymorphisms in normal families, families with the fragile X syndrome, and other families with X linked conditions.

Multipoint linkage analysis was undertaken with eight Xq cloned DNA sequences which identify one or more restriction fragment length polymorphisms in 26 families. These families comprise seven phase known normal families with three or more males in the third generation, seven families segregating for haemophilia B, one large family with dyskeratosis congenita, and 11 families with the fragile X syndrome. Phase known meioses informative for three or more loci supported the order centromere--DXYS1--DXS107--DXS102, DXS51--F9--FRAXA--DXS15, DXS52, F8--Xqter in each group of families studied. One of the normal families was segregating for protan colour blindness and showed a phase known recombination which would support the order centromere--F9--DXS52--CBP--Xqter. With the exception of DXYS1, all of these sequences have been localised to Xq27----qter by in situ hybridisation or hybridisation to Xq fragment panels, and on this basis should lie within 20 cM of one another. No recombination was observed between the sequences localised to Xq28, namely DXS52, F8, and DXS15 (between DXS15 and DXS52 Z = 12.25 at theta = 0 with confidence limits of 0 to 5 cM). However, an excess of recombination was apparent in the region of FRAXA with maximal lod scores as follows: F9 versus FRAXA (Z = 2.05, theta = 0.19), DXS52 versus FRAXA (Z = 1.85, theta = 0.26), and DXS15 versus FRAXA (Z = 1.33, theta = 0.27). No consistent differences were observed in the frequency of recombination when families with the fragile X syndrome were compared with normal families or families segregating for other X linked conditions. These results are compared with other published work and support the conclusion that although measurable linkage exists between these flanking markers and FRAXA, the intervals as measured by the frequency of meiotic recombination will seriously limit their clinical usefulness.

Chromosome Mapping↗
PubMed1987

Linkage of the tuberous sclerosis locus to a DNA polymorphism detected by v-abl.

Linkage analysis was undertaken in six families with tuberous sclerosis (TS) using a restriction fragment length polymorphism detected by v-abl. No recombinants were observed in 13 informative meioses (four phase known) giving a maximum lod score of 3.18 at zero recombination (confidence limits 0 to 0.15). This provides further evidence for the assignment of TS to 9q34 and should facilitate cloning of the structural gene, genetic counselling, and first trimester prenatal diagnosis.

DNA↗