Further studies on the effect of nucleotides upon expression of the folate sensitive fragile sites have confirmed that high concentrations of thymidine (300 mg/l) but not BrdU (600 mg/l) induce these fragile sites. Induction by thymidine can be suppressed by addition of cytidine in a dose response manner. Studies on other nucleotides suggest that guanosine, but not adenosine or cytidine, can induce the fragile sites. The previously hypothesised model for the DNA at a fragile site as a naturally occurring polypurine/polypyrimidine sequence which becomes amplified is further developed.

Adenosine↗

PubMedDate not supplied

X-linked mental retardation with dystonic movements of the hands.

We describe a family with a syndrome of mental retardation, dystonic movements of the hands and dysarthria inherited in an X-linked recessive pattern. DNA marker studies gave a maximum lod score of 2.11 at theta of 0.00 for DXS41 with a likely localization of the gene to Xpter----Xp21.

Adolescent↗

PubMedDate not supplied

Prenatal diagnosis of the fragile X--the Australasian experience.

Identification of increasing numbers of females heterozygous for fragile X linked mental retardation together with improved genetic counselling is creating a growing demand for prenatal diagnosis of fra(X). However, present cytogenetic techniques are somewhat unreliable and our collaborative approach has endeavoured to improve quality of cell culture systems and the sensitivity of fra(X) detection. Since 1985 we have exchanged cell cultures between our laboratories for verification of diagnostic results and comparison of induction techniques and have benefitted from larger numbers of cells scored for fra(X). Our 50 cases represent almost all of such studies undertaken in Australasia (Australia and New Zealand). Ten cases were unequivocally fra(X) positive; there was discrepancy between laboratories in 4 cases and one false-negative case. We propose a protocol to enhance fra(X) detection and conclude that, provided care is exercised, couples at risk of a fra(X) pregnancy can benefit from prenatal cytogenetic diagnosis.

Amniocentesis↗

PubMedDate not supplied

Linkage studies with the gene for an X-linked syndrome of mental retardation, microcephaly and spastic diplegia (MRX2)

A family in which a gene (MRX2) is segregating for an X-linked syndrome of mental retardation, short stature, microcephaly, brachycephaly, spastic diplegia, small testes and possible intra-uterine growth retardation is described. There are 7 clearly affected males and one possibly affected infant in the family. The obligate carriers are normal. Linkage studies show a suggestion of linkage to loci near the centromere. The maximum lod score was 2.10 at theta = 0.11 for DXYS1, assuming the possibly affected male carried the MRX2 gene. There were lower lod scores suggestive of linkage with DXS7 (theta = 0.14; z = 1.29) and DXS94 (theta = 0.11; z = 1.22).

Adolescent↗

PubMedDate not supplied

A family with the Coffin Lowry syndrome revisited: localization of CLS to Xp21-pter.

We revisited a family with the Coffin-Lowry syndrome (CLS) first reported by Procopis and Turner in 1972. Twelve affected members are now known in 3 generations of which 9 were seen personally. DNA marker studies supported X-linkage with localization of CLS to Xp near DXS43 at p22.2-22.1 (theta = 0.001 Z = 2.71). Such linkage is reinforced by positive lod scores for DXS28 (theta = 0.00, Z = 0.90) and for DXS84 (theta = 0.09, Z = 1.56). Recombination with DXS84 and DXS164 places CLS distal to DMD in Xp21-pter.

Adult↗

PubMedDate not supplied

Linkage between the fragile X and F9, DXS52 (St14), DXS98 (4D-8) and DXS105 (cX55.7).

Linkage data using the markers F9, DXS105 (cX55.7), DXS98 (4D-8) and DXS52 (St14) are presented from 22 kindreds segregating with the fragile X. Two-point linkage analysis was carried out taking into account cytogenetic results and penetrance classes defined by mental impairment status of mothers. Recombination frequencies (theta) corresponding to the maximum z scores (z) were obtained between F9 (z = 3.48, theta = 0.18), DXS105 (z = 5.06, theta = 0.07), DXS98 (z = 4.79, theta = 0.01) and DXS52 (z = 6.44, theta = 0.09) and the fragile X. Recombination frequencies between marker loci in fragile X families are also presented. These recombination frequencies need to be combined with those from other studies in order to determine the best estimates of map distances for use in genetic counselling, until markers closer to the fragile X, or at the fragile X, can be used. Most potential fra(X) heterozygotes were informative for flanking markers using the above 4 probes. Carrier risks were determined by 3-point analysis using informative flanking markers, taking into account cytogenetic results. Low level fra(X) expression occurred in 2 probable non-carriers; emphasising the need for extreme caution in the interpretation of low rates of expression.

Factor IX↗

PubMedDate not supplied

Acinic cell carcinoma metastatic to the brain: case report and ultrastructural study.

We report a case of isolated cerebral metastasis from an acinic cell carcinoma, which arose in minor salivary glands 20 years previously. The clinical, pathologic and ultrastructural features are described, together with a review of the literature, which suggests that this is an unusual occurrence.

Brain Neoplasms↗

PubMedDate not supplied

Persistent truncus arteriosus operated during infancy: long-term follow-up.

Between July 1974 and October 1988 19 consecutive infants (mean age 2.7 months, range 5 days to 11.7 months) underwent surgical correction for persistent truncus arteriosus by one surgeon (J.L.M.). Continuity between the right ventricle and pulmonary arteries was achieved with an antibiotic-sterilized aortic homograft (diameter 13-18 mm) together with patch closure of the ventricular septal defect. There were 3 early postoperative deaths (16%): 1 patient had severe aortic regurgitation, the other 2 had preoperative cardiac arrests. Of the latter, 1 had suffered severe cerebral damage, and the other developed recurrent pulmonary hypertensive crises and low cardiac output. The 16 survivors have been followed for 3.1-17.3 years (mean 7.8 years). Four patients required subsequent replacement of the homograft for stenosis, aortic valve replacement for regurgitation, or both (3.0, 4.0, 8.5, and 12.0 years postoperatively). Of the 16 survivors, 15 are in NYHA class I. Of the 13 patients who have not had aortic valve surgery, 9 have no evidence of stenosis or regurgitation. In the 14 children with the original homograft the median of the residual peak gradient across the right ventricular outflow tract is 15 mmHg (range 10-40 mmHg), and no patient has severe homograft regurgitation at follow-up. Repair of persistent truncus arteriosus has been achieved with low early mortality and no late mortality, which reflects excellent long-term function of the homograft. Furthermore, if truncal valve function is good at presentation, patients are unlikely to require aortic valve surgery.

Aortic Valve↗

PubMedDate not supplied

New ultrasound methods to quantify regional myocardial function in children with heart disease.

From a temporally resolved radio-frequency data set, a series of new developing indices of regional myocardial deformation can be measured. These may be important new data sets to quantify regional radial and long axis function of the left or right ventricle in children with acquired or congenital heart disease. Using color Doppler methodology unidimensional regional myocardial strain rates (SR) and natural strain (e) can now be calculated from local myocardial velocity data sets. Normal regional velocity, SR, and e values have already been determined in older children and should form the database for studies into acquired or congenital heart disease in this age group. Neonatal and infant values have yet to be determined. This article will present preliminary data on the potential clinical value of ultrasonic regional SR and e imaging in children and will discuss the close interrelation of these new regional function parameters with an alternative approach to quantification: the measurement of local cyclical changes in integrated backscatter levels.

Blood Flow Velocity↗

PubMedDate not supplied

Genomic structure and expression analysis of the spastic paraplegia gene, SPG7.

SPG7 is a newly identified gene involved in an autosomal recessive form of hereditary spastic paraplegia (HSP), a genetically heterogeneous group of neurodegenerative disorders. This gene encodes a protein characterized as a nuclear-encoded mitochondrial metalloprotease. The present report describes the genomic structure of the SPG7 gene. It is organized into 17 exons ranging from 78 to 242 bp and spans approximately 52 kb within three overlapping cosmids. The exon/intron boundaries and all splice junctions are consistent with the published consensus sequences for donor and acceptor sites. The provided genomic structure of SPG7 should facilitate the screening for mutations in this gene in patients with HSP and other related mitochondrial disease syndromes. SPG7 has been mapped to chromosome 16q24.3, a region of frequent loss of heterozygosity (LOH) seen in sporadic breast and prostate cancer. We have performed single-strand conformation polymorphism analysis of ten exons of this gene in a number of sporadic breast cancer samples showing LOH at 16q24.3. No mutations were detected; only single nucleotide polymorphisms were observed in exon 11, intron 7, intron 10 and intron 12. An expression analysis study has revealed the differential expression of SPG7 mRNA in various tissues and at different developmental stages.

ATPases Associated with Diverse Cellular Activitie↗