Some causes of genotypic and phenotypic discordance in monozygotic twin pairs

Abstract

The use of the adjective “identical” rather than monozygotic leads to misunderstandings about the biology of monozygotic twinning. Most monozygotic twin pairs are not identical; there may be major discordance for birth weight, genetic disease, and congenital anomalies. These indicate that postzygotic events may lead to the formation of two or more cell clones in the inner cell mass and early embryo that actually stimulate the monozygotic twinning event. There is also evidence that there may be unequal allocation of numbers of cells to the monozygotic twins; this may have widespread implications for the cascade of developmental events during embryogenesis, formation, and vascularization of the placenta. Large‐scale zygosity testing at birth could be the template for analysis of twin outcomes and their biologic causes. © 1996 Wiley‐Liss, Inc.

Cellular imaging demonstrates genetic mosaicism in heterozygous carriers of an X-linked ciliopathy gene

“…Uneven lyonization has been known as a possible cause for a discordant phenotypical expression of X-linked diseases. 36 This hypothesis implies that the affected cone cell has a skewed inactivation predominantly of the Mosaic disruption in XLRP carriers with the AOSLO S Pyo Park et al Figure 2 High-resolution SD-OCT scans through the fovea of the five XLRP carriers. SD-OCT images of (a) subject 1, (b) subject 2, (c) subject 3, (d) subject 4 and (e) subject 5.…”

“…Uneven lyonization has been known as a possible cause for a discordant phenotypical expression of X-linked diseases. 36 This hypothesis implies that the affected cone cell has a skewed inactivation predominantly of the wild-type X-chromosome, whereas the unaffected cone cell either has a random X-inactivation or a predominant inactivation of the X-chromosome carrying the mutant gene. The RPGR gene, which account for about 70% of all XLRP cases, is located in chromosomal region Xp21.1, spans 172 kb and was initially reported to contain 19 exons.…”

Infants with Bochdalek diaphragmatic hernia: Sibling precurrence and monozygotic twin discordance in a hospital‐based malformation surveillance program

“…Genetic basis for discordance in MZ twins-Phenotypic discordance between monozygotic twins can arise through a number of different mechanisms, both genetic and nongenetic [Machin, 1996]. Post-zygotic de novo mutations, as well as epigenetic differences are mechanisms proven to underlie MZ twin discordance [Kondo et al, 2002;Weksberg et al, 2002].…”

Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders

“…[16][17][18] Cause of discordance between MZ twins A number of case reports have revealed that phenotypic discordance between MZ twins can be arisen from several kinds of genetic or epigenetic differences, which are inter-correlated each other. 19 For example, expansion of triplet repeat can alter DNA methylation status, and reduced DNA methylation of transposon can cause transposition and finally causes disruption of a gene. Thus, dichotomy of 'genetic' and 'epigenetic' is difficult, and only a tentative classification is given below.…”

“…Since the percentage and the tissue distribution may differ between the MZ twins, mosaicism of chromosomal abnormality can cause discordance between MZ twins. Machin 19 extensively reviewed the MZ twin cases with discordant phenotype caused by chromosomal abnormalities. They reviewed 16 pairs of MZ twins discordant for Turner syndrome.…”