In an attempt to understand the nature of the mutational event leading to the fra(X) syndrome, we have searched for sporadic cases in 3 populations: affected males, affected females, and non-affected transmitting females. In all 3 populations there was a dearth of isolated cases, and the reasons for this are discussed.

Female↗

PubMedDate not supplied

Fragile X syndrome and nephrogenic diabetes insipidus.

We describe a man with the fra(X) syndrome and nephrogenic diabetes insipidus. The disease loci for both conditions are in the region Xq27.3-q28. This is the first report of the fra(X) syndrome associated with another X-linked disorder. Analysis of DNA markers suggested that the association in this man was coincidental.

Diabetes Insipidus↗

PubMedDate not supplied

A new syndrome with mental retardation, short stature and an Xq duplication.

We describe a new X-linked syndrome of marked short stature, severe intellectual handicap and an unusual facial appearance. High resolution prometaphase banding showed affected males to have an X chromosome tandem duplication; their karyotypes were designated 46,dup(X) (q13.1-q21.1)Y. In carrier females the abnormal X chromosome was late replicating. To verify the duplication, gene dosage studies were performed using an enzyme assay and DNA techniques. Prenatal diagnosis is available for carrier females using chromosome analysis of amniocytes or chorionic villi.

Child↗

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

Screening for the fragile X: how many cells should we analyse?

Since nationwide screening for the fragile X would involve the analysis of thousands of individuals within a short period of time, the number of cells, N, which should be analysed is of fundamental importance. When selecting N, the crucial parameter should be the degree of expression of the fragile site in the affected individuals in the population to be screened. However, this degree of expression is not known, and for routine diagnostic purposes, N = 100 has been accepted by many centers. By taking data from two large series of affected males/females with a known degree of expression (one series from New South Wales, one from Belgium), we have estimated the fraction of affected males/females which would have been missed if the two series were rescreened with the analysis of less than 100 cells. Assuming that the degree of expression within these two series is similar to the degree of expression in all affected individuals within the two populations, the results indicate that a reduction of N in a screening program, say from 100 to 50 cells, would reduce the detection rate between 1 and 5%. The reduction would be greater in females than in males, and greater in the Belgian than in the Australian population.

Cell Count↗

PubMedDate not supplied

Fragile (X) expression, age and the degree of intellectual handicap in the male.

The proportion of cells expressing the fra(X) was compared to the guardian's opinion of who was the "brighter" in 31 sibships of 2 or more affected males. Six fra(X) positive males in the normal workforce were compared in a similar way to other affected relatives. A correlation was found between lower values of expression and "brightness" by the Wilcoxson signed rank test (less than 0.01, 2-tail). A decline in fra(X) expression occurs with age. Some apparently normal non-expressing transmitting males may be accounted for by these findings.

Adult↗

PubMedDate not supplied

Is there a fragile(X) negative Martin-Bell syndrome?

During the course of the preventative screening program for the fra(X) syndrome, we identified 32 men with the phenotype but who were fra(X) negative. These were reviewed and none fitted the full criteria, so we were unable to confirm the existence of the fra(X) negative Martin-Bell syndrome. The literature and 4 families previously thought to have the fra(X) negative Martin-Bell syndrome were also reviewed. We were unable to make a concrete diagnosis of the fra(X) negative Martin-Bell syndrome.

Adult↗

PubMedDate not supplied

A non-syndromal form of X-linked mental retardation (XLMR) is linked to DXS14.

An analysis of the linkage of a non-syndromal form of X-linked mental retardation (MRX1) with a number of markers on the X chromosome was performed in a large pedigree. The affected males had moderate mental retardation; in all other clinical respects and cytogenetically they were normal. No recombinants were observed between the MRX1 gene and the marker DXS14 (p58.1) located at Xp11-cen (Z (max.) = 2.12 at theta = 0.00). Recombination was observed between the MRX1 gene and the markers DXS7 and DXYS1 which flank DXS14. This form of XLMR maps to the centromeric portion of the X-chromosome.

Chromosome Mapping↗

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

Investigation of the twinning rate in families with the fragile X syndrome.

An excess of twins in families with the Martin-Bell or fra(X) syndrome was noted previously in one family study [Fryns, 1986]. We tried to confirm this observation in a second large sample of families from a different population. We calculated the number of twin births among the total number of live births of known obligate carriers found in fra(X) families ascertained in New South Wales, Australia. We only included births of known sex and excluded triplets. There were 5 male pairs, 3 female pairs and 9 unlike sex pairs of twins born among 752 live births. Thus the twining rate was 1/44 per live birth. We compared this rate to that found in two different types of individuals: 1) the rate of 1/96 which was obtained from the 1985 vital statistics for New South Wales, and 2) the rate 1/75 obtained from a sample of live births of obligate carriers with hemophilia A. The increase in twinning among heterozygotes with the fra(X) was highly significant when compared to the census data (p less than 0.001). However, it was not significantly different from that in the hemophilia data (p less than 0.05) which were collected in the same way as in the fra(X) families.

Epidemiologic Methods↗