Monozygotic twins of opposite sex

Although discordant karyotypes are known in identical twins, cases involving differences in sex phenotype are rare. We studied identical twins with the 46,XY karyotype - a male with mixed gonadal dysgenesis and a female with "pure" gonadal dysgenesis. The testis-determining SRY gene was present in DNA from both twins but no mutations were detected in the SRY conserved motif. Monozygosity was indicated by short tandem repeat polymorphism analysis. These observations could be attributed to (i) mutation and mosaicism involving "downstream" sex-determining loci, (ii) variable penetrance of genes such as DSS/NR0B1, duplication of which can disrupt the male-determining pathway, or (iii) occurrence of cryptic 45,X gonadal cell lines.     

Monozygotic twins reveal germline contribution to allelic expression differences

Variation in the level of gene expression is a major determinant of a cell's function and characteristics. Common allelic variants of genes can be expressed at different levels and thus contribute to phenotypic diversity. We have measured allelic expression differences at heterozygous loci in monozygotic twins and in unrelated individuals. We show that the extent of differential allelic expression is highly similar within monozygotic twin pairs for many loci, implying that allelic differences in gene expression are under genetic control. We also show that even subtle departures from equal allelic expression are often genetically determined.     

The probability of dizygosity of phenotypically concordant twins.

A basic element in the determination of the zygosity of a twin pair is the proportion of genotypically concordant pairs among the dizygotic pairs. Two methods to derive this proportion are in common use: the first method requires a laborious enumeration of parental genotypic mating types, and the second method relies on a set of formulas, one for each of the possible combinations of genotypes of two full sibs. In this paper the relation between both methods is uncovered. The set of formulas of the second method is reduced to a single general formula, of which the connection with the ITO method (Li and Sacks 1954) is indicated. By applying both methods in turn to an example concerning the MNS blood group system (Fisher 1951), Fisher's way of performing the calculations according to the first method is unraveled, and the preferability of the second method is made clear. Next, formulas are derived for the probability of genotypic or phenotypic concordance of dizygotic twins when direct information on the genotype or phenotype of one of the parents is available. The case of an X-linked locus is also considered. To facilitate applications, tables are given.     

Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles

The exploration of copy-number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic makeup between twins derived from the same zygote represent an irrefutable example of somatic mosaicism. We studied 19 pairs of monozygotic twins with either concordant or discordant phenotype by using two platforms for genome-wide CNV analyses and showed that CNVs exist within pairs in both groups. These findings have an impact on our views of genotypic and phenotypic diversity in monozygotic twins and suggest that CNV analysis in phenotypically discordant monozygotic twins may provide a powerful tool for identifying disease-predisposition loci. Our results also imply that caution should be exercised when interpreting disease causality of de novo CNVs found in patients based on analysis of a single tissue in routine disease-related DNA diagnostics.     

Monozygotic twins with Turner's syndrome and mos 45,X/46,X,r,(Y)

A pair of monozygotic twins with Turner's syndrome was studied using combined cytogenetic techniques and a mos 45,X/46,X,r(Y) was demonstrated in both. One of the twins presented clitoral hypertrophy. Surgery was performed and uterus, bilateral Fallopian tubes, bilateral epididymis and bilateral streak gonads with a small nodule of testicular tissue containing numerous seminiferous tubules were found in both.     

Kleine-Levin syndrome: a series of case reports

Kleine-Levin syndrome (KLS) is an intriguing, severe, homogenous disease, with well defined clinical features, but no clear cause or treatment. Therefore studies on KLS were done exclusively with case report or series. There are limited systemic study comparing KLS with controls on phenomenology, cause, investigations and management. We report four cases of KLS presented to us along with core symptoms, hypomanic and catatonic features. Response to treatment also different with one case responded to lithium while others required combination of therapy. KLS is still evolving disorder having cluster of varying symptoms and response to treatment. This needs further exploration and higher studies

     

Monozygotic twins discordant for constitutive BRCA1 promoter methylation, childhood cancer and secondary cancer

We describe monozygotic twins discordant for childhood leukemia and secondary thyroid carcinoma. We used bisulfite pyrosequencing to compare the constitutive promoter methylation of BRCA1 and several other tumor suppressor genes in primary fibroblasts. The affected twin displayed an increased BRCA1 methylation (12%), compared with her sister (3%). Subsequent bisulfite plasmid sequencing demonstrated that 13% (6 of 47) BRCA1 alleles were fully methylated in the affected twin, whereas her sister displayed only single CpG errors without functional implications. This between-twin methylation difference was also found in irradiated fibroblasts and untreated saliva cells. The BRCA1 epimutation may have originated by an early somatic event in the affected twin: approximately 25% of her body cells derived from different embryonic cell lineages carry one epigenetically inactivated BRCA1 allele. This epimutation was associated with reduced basal protein levels and a higher induction of BRCA1 after DNA damage. In addition, we performed a genome-wide microarray analysis of both sisters and found several copy number variations, i.e., heterozygous deletion and reduced expression of the RSPO3 gene in the affected twin. This monozygotic twin pair represents an impressive example of epigenetic somatic mosaicism, suggesting a role for constitutive epimutations, maybe along with de novo genetic alterations in recurrent tumor development.     

Alport's syndrome in twins]

Alport's syndrome consists of hereditary nephritis, often progressing to renal failure, and variable neural hearing loss. It was diagnosed in dizygotic twins, aged 32 years, suffering from nephropathy manifested by microscopic hematuria, proteinuria and chronic renal failure, accompanied by hearing loss and ocular disorders (observed in both retina and lenses). Gothic palate has been noted in both patients. Glomerulitis was diagnosed for the first time at the age of 11 and 12 years, respectively. Hearing loss began in one brother 10 years later, and in another 11 years later. Renal failure developed much later. Diagnostic problems were due to the fact, that streptomycin was used in childhood (another cause of hearing loss?) and to the lack of any symptoms of Alport's syndrome in other members of the family.     

HLA-DR typing in identical twins with insulin-dependent diabetes: difference between concordant and discordant pairs.

A total of 106 pairs of identical twins, of whom 56 were concordant and 50 discordant for insulin-dependent diabetes, were typed for HLA-DR. In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. This was therefore the first demonstration of a genetic difference between concordant and discordant identical twin pairs. These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone.     

Laurence-Moon-Biedl syndrome in presumably identical twins

Summary A Saudi Arabian family with 3 cases of Laurence-Moon-Biedl syndrome, 2 of whom are presumably identical twins, is presented. Although it is generally accepted that this condition is inherited as an autosomal recessive trait, no conclusive data exist in the literature to support this theory.

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Zusammenfassung Wir präsentieren eine saudiarabische Familie, in der 2 Mitglieder vermutlich eineiige Zwillinge sind. In dieser Familie finden sich 3 Fälle von Laurence-Moon-Biedl-Syndrom. Wenngleich allgemein angenommen wird, daß dieser Zustand als autosomales recessives Merkmal vererbt wird, existieren hierfür keine überzeugenden Daten in der Literatur.