FAMILIAL COMPLEX TRANSLOCATION INVOLVING CHROMOSOMES 1,4,9,20
Vazharova R1, Stoyanova V2, Ghenev E2, Toncheva D1
*Corresponding Author: Toncheva D. Department of Medical Genetics, Medical University Sofia, 2 Zdrave str, 1431 Sofia, Bulgaria Tel/Fax: + 359 2 9520357 email: draga@spnet.net
page: 41

DISCUSSION

 

In this study we found a very rare complex chromosomal rearrangement in a fetus and his mother. The result was optimistic since the mother was phenotypically normal and the ultrasound examination of the fetus at 22 weeks of gestation showed normal fetal growth and no abnormalities.
No malformed children had been born in the reported family and other family members reported no repeated miscarriages. Since none of the abortions were examined, it is not known whether they carried unbalanced chromosome complements (Fig.4).
Familial balanced complex chromosomal rearrangements are found very rarely in the general population. Cases with complex chromosomal rearrangements involving four chromosomes and showing familial transmission (Table1) have been mainly discovered through children with dysmorphic features and mental retardation.

Table1. Inherited familial balanced complex chromosomal rearrangements, involving four chromosomes


Reference

Involved chromosomes

Breakpoints

origin

Reasons for ascertainment

Mode of segrega
tion

De Grouchy et al,
1972

3, 10, 1, 12

Not stated exactly:
3p+, 10q-. 12p+, 1q-

Maternally and paternally derived

Balanced translocations in three generations.

Adj1
Alt

Handmaker et al, 1975

2, 4, 7, 8

Not stated exactly:
2p-, 4p-, 7p+, 8q+

Maternally
derived

Multiple congenital malformations

Adj1

Bijlsma et al, 1978

2, 6, 7, 12

2q35, 6q23, 7p22, 12p11

Maternally
derived

Boy with partial trisomy 12p. Complex translocation in three generations of the family

Adj1

Bass and Sparkers 1979

7, 10, 14, 21

7q11, 10q22, 14qter>cen>21qter

Great-grand maternally derived

Family ascertained through the boy with Down’s syndrome and Robersonian translocation

Adj 2

Simoni et al,
1979

2, 9, 12, 18

2q33, 9p24, 12p13, 18q21

Maternally derived

A child with
multiple congenital malformations

Adj1

???r et
al,
1981

6, 7, 8, 12

6q27, 12q21,7p14, 8q22, 8q13

Great-grand maternally derived

Reciprocal translocation and inverted insertion in three healthy generations of the family

Alt

Van der
Burgt et al,
1992

5, 11, 12, 16

5q34, 11p15.3, 12p13.1, 12q12, 16p11

maternally derived

A child with
multiple congenital malformations

Adj1

Gorski et al,
1988

2, 5, 7, 9

2q33, 5p13, 5q32, 7q32, 7q34, 9p24

Not tested

multiple congenital malformations

Adj1

Adj 1 - adjacent type 1; Alt - alternative

In most pedigrees with segregation of a complex rearrangement through several generations described so far, not only the transmission of the complete balanced rearrangement but also inheritance of only part of the rearrangement, in balanced and unbalanced forms, have been observed [5,6,11]. To our knowledge only Meer et al 1981 [12] have not found any unbalanced karyotypes within a large pedigree. They reported only balanced and normal karyotypes among live births.
A small number of BCT are detected during prenatal diagnosis. To our knowledge the reported case is the second with familial 4-way balanced chromosome translocation identified during prenatal diagnosis. BCT observed in cultured amniocytes are a serious problem in genetic counseling and it is difficult to predict the outcome of pregnancy and the chances for normal development especially in the de novo cases [Table 2].

Table 2 Balanced complex translocations involving four chromosomes identified during prenatal diagnosis.


Reference

Involved chromosomes

Number of breaks / breakpoints

Sex

Phenotype

ih / dn / nt

Kim et al(1986)

t(4; 6; 15; 16)

4q31.2, 6q25, 15q23, 16p13.1

M

Growth retardation

dn

Sikkema-Raddatz (1995)

t(3; 4; 10; 17)

3p12, 3q26.2, 4p14, 4q12, 10p12, 10q21, 17q23

M

Autopsy no abnormalities

dn

Mercier et al (1996)

t(2q; 3p; 4q; 13q)

5 breaks

F

Congenital abnormalities

dn

Phelan MC (1998)

6, 12, 14 and 16

9 breaks

F

Congenital abnormalities

dn

Lee MH et al (2002)

t(5; 16; 10;18)

5q13; 16q22; 10q11.2; 18q21)

F

normal development

ih
maternally derived

Present report

1,4, 9 and 20

4 breaks: 1q32, 4p13, 9p13, 20p13

M

Normal ultrasonographic features

ih
maternally derived

Ih- inherited, dn - de novo, nt - not tested, F- female, M - male.

In the reported family the revealed balanced complex translocation is associated with reproductive problems. Spontaneous abortions in the family have not been studied cytogenetically and it is not known if they carried unbalanced chromosome complements. Some of the families reported in the literature had only spontaneous abortions and others - only abnormal children.
Various types of segregation of the t(1;4;20;9) will result in different karyotype configurations. Since the observed translocation is a 4-way with one breakpoint on each involved chromosome it is in some instances similar to balanced reciprocal translocations involving 2 chromosomes that form quadrivalent during meiosis. The formation of a octavalent during gametogenesis gives the possibility of formation of severely unbalanced gametes. The alternate type of segregation, without cross-over in the interstitial segments will result in all gametes having the balanced rearranged or the normal chromosome complement. Any adjacent (-1 or -2) without cross-over or the alternate type with cross-over in one interstitial segment will result in all gametes being unbalanced, having both a duplication and a deficiency. Recombinations are not expected.

Fig4. Pedigree of the reported family. The carriers of the balanced translocation are indicated by arrows


Because the new born child is male, his growth will be followed up after birth and we will particularly pay attention to his puberty, because as Rodriquez et al 1985 [9], Chandley et al 1975[7], Josef et al 1982[8] cited male carriers of complex chromosomal rearrangements involving four chromosomes have an increased risk of being infertile.




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