Correspondence

More on Primary Biliary Cirrhosis in Monozygotic Twins

N Engl J Med 1995; 332:336February 2, 1995

Article

To the Editor:

The letter “Discordant Occurrence of Primary Biliary Cirrhosis in Monozygotic Twins” (October 6 issue)1 reflects a common misconception regarding the determination of zygosity. Although the sisters described in the report are twins, inadequate evidence of monozygosity was given. Identifying HLA haplotypes does not establish zygosity. The sisters have the same HLA haplotypes, as do 25 percent of siblings. They are also the same sex, as are 50 percent of dizygotic twins.

Monozygotic twins are formed from a single conceptus and therefore have the same member of each pair of chromosomes from each parent. Testing for concordance for markers from several different chromosomes can demonstrate that the probability of monozygosity is greater than 99 percent,2 provided one parent is heterozygous at each locus and no technical errors are made in typing the markers.

Proof of the sisters' monozygosity would provide evidence that an environmental trigger precipitated the clinical manifestations. If they are dizygotic twins, however, the discordant occurrence of primary biliary cirrhosis could represent the inheritance of other genes that modify the response to a common environmental stimulus in two siblings with the same HLA haplotypes. Establishment of zygosity is crucial to distinguish between these possibilities.3

Chris Friedrich, M.D., Ph.D.
Johns Hopkins University School of Medicine, Baltimore, MD 21287

3 References

1. 1

   Kaplan MM, Rabson AR, Lee Y-M, Williams DL, Montaperto PA. Discordant occurrence of primary biliary cirrhosis in monozygotic twins. N Engl J Med 1994;331:952-952
   Full Text | Web of Science

2. 2

   Das Chaudhuri AB. Efficient sequential search of genetic systems for diagnosis of twin zygosity. Acta Genet Med Gemellol (Roma) 1991;40:159-164
   Web of Science | Medline

3. 3

   Machin GA. Twins and their zygosity. Lancet 1994;343:1577-1577
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We appreciate the comments of Dr. Friedrich. The two sisters have been referred to as identical twins since birth. This plus the fact that they have identical HLA haplotypes makes it probable that they are monozygotic twins. We agree that more extensive genetic testing would be required to approach the 100 percent probability that Dr. Friedrich desires.

Marshall Kaplan, M.D.
Arthur R. Rabson, M.D.
New England Medical Center, Boston, MA 02111

Citing Articles (2)

Citing Articles

1. 1

   Carlo Selmi, Marlyn J. Mayo, Nancy Bach, Hiromi Ishibashi, Pietro Invernizzi, Robert G. Gish, Stuart C. Gordon, Harlan I. Wright, Bruce Zweiban, Mauro Podda, M.Eric Gershwin. (2004) Primary biliary cirrhosis in monozygotic and dizygotic twins: Genetics, epigenetics, and environment. Gastroenterology 127:2, 485-492
   CrossRef

2. 2

   JJ FELD, EJ HEATHCOTE. (2003) Epidemiology of autoimmune liver disease. Journal of Gastroenterology and Hepatology 18:10, 1118-1128
   CrossRef