Clinical Genetics 1977: 12: 39-42
Familial occurrence of chromosome variant 17ph+ KLECZKOWSKA Department of Clinical Biochemistry, Cytogenetic Laboratory, Institute of Pediatrics, Medical Academy, Krakbw, Poland ELZBIETA K U B I E ~A N D
ALICJA
A structural chromosome variant 17ph+ was found in a high genetic risk family. The authors consider the possibility of a causal connection between minor structural changes in the karyotype and congenital defects appearing in one member of the family. Received 30 November 1976, revised 23 February, accepted f o r publication 1 March 1977
The occurrence of structural chromosome variants has recently been interpreted as a population variable (Bochkov et al. 1974, Hamerton et al. 1975, Muller et al. 1975, Nielsen & Sillesen 1975). A marker chromosome 17p described by Sandstrom & Jenkins (1973, 1974) was considered from a similar point of view. However, some authors have demonstrated a relation between structural chromosome variant 17-18 and the occurrence of congenital malformations (Littlefield et al. 1966, Daly 1970, Battaglia et al. 1971). In the present paper, the authors describe heterozygotic inheritance in two generations of structural chromosome variant 17ph+ in a high genetic risk family. Material and Methods
The family with the chromosome variant was discovered in the course of studies carried out in a group of high genetic risk families, i.e. those in which the birth of at least one child with multiple congenital malformations had been noted. The product
of the second pregnancy in the family under consideration was a girl who was born with a high-arched palate, congenital heart defect and oedema of both hands and legs, and who died in the second week of life. The two remaining siblings were not malformed. The father and mother were 42 and 30 years old, respectively, when the malformed baby was born. All four members of the family were karyotyped. Mitotic chromosomes were routinely stained, according to Schnedl’s method (1971). Results
The results of the cytogenetic survey of the family under consideration are summarized in Table 1. One morphologically anomalous chromosome belonging to the 17th pair was noted in the phenotypically normal mother and son. It was found in a high percentage of the metaphases analyzed (see Table 1). A secondary constriction was usually observed on its short arm, and was clearly visible in prophase stages. According to the
KUBIEI(I A N D K L E C Z K O W S K A
40
Table 1 Cytogenetic survey of the family S Percentage of metaphases with structural chromosome variant 17ph+
Patient
Number of cultures
Number of metaphases analyzed
Father
1
100
Mother
2
125
62.4
46,XX,17ph +
Son
2
132
40.9
46,XY,17ph+
Daughter
1
100
-
E
-E
16-15
16-lE
E
Karyotype
46,XX
16-18
E
16-1 8
E
16-18
E
16-1
--E
16-1 8
(i li II) E
E
E
16-12
lb-iO
16-18
Flg. 1. Partial karyotype of son (routine Giemsa staining). Note a structural chromosome variant in the 17th pair.
I .
8
Flg. 2. Giemsa banding pattern in a partial karyotype of mother. Note the same structural chromosome variant in the 17th pair as in Figure 1.
FAMI LIAL OCC UR R ENCE 0F
C H ROMO S O M E V A R I A N T 17ph +
Paris Conference (1971), this chromosome was described as a structural variant 17ph+ (Figs. 1 and 2 ) . This chromosome variant persisted in repeated lymphocyte cultures from the peripheral blood of mother and son, while simultaneously performed control cultures did not reveal similar changes.
Discussion
The structural change in the short arm of chromosome No. 17 has been interpreted by some authors as being due to satellites o n this chromosome (Berg et al. 1969, Daly 1970, Battaglia et al. 1971), while others have considered it t o be a secondary constriction (Sandstrom & Jenkins 1973, 1974). Our observations led us to the conclusion that it is a secondary constriction 17ph+, as this chromosome showed no tendency to association with satellited chromosomes of D and G groups. The structural chromosome variant 17ph+, as it appeared in the family investigated, was inherited heterozygotically from mother to son without phenotypic features. Berg et al. (1969) stressed the absence of phenotypic features connected with the homozygotic inheritance of the 17p variant. However, one of the members of the family described by these authors, in whom the heterozygotic variant 1 7 p was found, had Klinefelter syndrome. Minor structural changes in chromosomes, e.g. variants such as enlarged satellites, duplication of satellites and uncoiled chromosomes, are regarded as a population variable (Bochkov et al. 1974, Hamerton et al. 1975, Miiller et al. 1975). Nevertheless, these structural variants have also been described as having causal connection with congenital defects (Daly 1970, Palmer & Schroder 1971, Kleczkowska & Kubien 1974). So far, our previous and also our
41
present observations incline us t o the opinion that in patients with minor structural changes of chromosomes there may be a predisposition to congenital defects.
References
Battaglia, E., G. Guanti, P. Barsanti & P. Petrinelli (1971). Chromosomal survey in 298 normal subjects and 1,253 cases of congenital disorders during 1966-1970. Acta Genet. med. (Roma) 20, 123-173.
Berg, J. M., J. A. Faunch, J. M. Pendrey, L. S. Penrose, M. A. C. Ridler & A. Shapiro (1969). A homozygous chromosomal variant. Lancet i, 531. Bochkov, N. P., N. P. Kuleshov, A. N. Chebotarev, V. I. Alekhin & S. A. Midian (1974). Population cytogenetic investigation of newborns in Moscow. Hum. Genet. 22, 139-152. Daly, R. F. (1970). Chromosome aberrations in 50 patients with idiopathic mental retardation and in 50 control subjects. J . Pediat. 77, 444453.
Hamerton, J. L., N. Canning, M. Ray & S. Smith (1975). A cytogenetic survey of 14,069 newborn infants. I. Incidence of chromosome abnormalities. Clin. Genet. 8, 223-243. Kleczkowska, A. & E. Kubieli (1974). Cytogenetic studies in congenital malformations. Congenital Malformations in Krakdw Region. Part 11. Project SRS-Pol-17-69 subventioned
according to the Polish-American Memorandum of Understanding, RSW “Prasa-KsiqzkaRuch” Ed., Krakow, pp. 23-44. Littlefield, L. G., W. S. Smith, D. A. Welter & A. J. Gatz (1966). Case study of a mentally retarded female exhibiting satellites on one No. 18 chromosome. Amer. J . Obstet. Gynec. 95, 1160-1162.
Miiller, H., P. H. Klinger & M. Glasser (1975). Chromosome polymorphism in a human newborn population. Cytogenet. Cell Genet. 15, 239-255.
Nielsen. 1. R: I. Sillesen (1975). Incidence of chromosome aberrations among 11,148 newborn children. Hum. Genet. 30, 1-12. Palmer, C. G. & J . Schroder (1971). A familial variant of chromosome 9. J . med. Genet. 8, 202-208.
Paris Conference (1971). Standardization in human cytogenetics. Birth Defects: Original Article Series VIII, No. 7 .
42
KUBIEI(I A N D K L E C Z K O W S K A
Sandstrom, M. McH. & E. C. Jenkins (1973). A 17p marker chromosome familial study. Ann. Genet. 16, 267-269. Sandstrom, M. McH. & E. C. Jenkins (1974). Cytological elucidation of a 17p marker chromosome. Curyologia 21, 307-313. Schnedl, W. (1971). Banding pattern of human chromosomes. Nature new Biol. 233, 93-94.
Address: Elibieta Kuhieh, Ph.D. Cytogenetic Laboratory Department of Clinical Biochemistry Institute of Pediatrics Medical Acudemy Wielicka St. 265 30-663 Krakdw, Poland
Familial occurrence of chromosome variant 17ph+ KLECZKOWSKA Department of Clinical Biochemistry, Cytogenetic Laboratory, Institute of Pediatrics, Medical Academy, Krakbw, Poland ELZBIETA K U B I E ~A N D
ALICJA
A structural chromosome variant 17ph+ was found in a high genetic risk family. The authors consider the possibility of a causal connection between minor structural changes in the karyotype and congenital defects appearing in one member of the family. Received 30 November 1976, revised 23 February, accepted f o r publication 1 March 1977
The occurrence of structural chromosome variants has recently been interpreted as a population variable (Bochkov et al. 1974, Hamerton et al. 1975, Muller et al. 1975, Nielsen & Sillesen 1975). A marker chromosome 17p described by Sandstrom & Jenkins (1973, 1974) was considered from a similar point of view. However, some authors have demonstrated a relation between structural chromosome variant 17-18 and the occurrence of congenital malformations (Littlefield et al. 1966, Daly 1970, Battaglia et al. 1971). In the present paper, the authors describe heterozygotic inheritance in two generations of structural chromosome variant 17ph+ in a high genetic risk family. Material and Methods
The family with the chromosome variant was discovered in the course of studies carried out in a group of high genetic risk families, i.e. those in which the birth of at least one child with multiple congenital malformations had been noted. The product
of the second pregnancy in the family under consideration was a girl who was born with a high-arched palate, congenital heart defect and oedema of both hands and legs, and who died in the second week of life. The two remaining siblings were not malformed. The father and mother were 42 and 30 years old, respectively, when the malformed baby was born. All four members of the family were karyotyped. Mitotic chromosomes were routinely stained, according to Schnedl’s method (1971). Results
The results of the cytogenetic survey of the family under consideration are summarized in Table 1. One morphologically anomalous chromosome belonging to the 17th pair was noted in the phenotypically normal mother and son. It was found in a high percentage of the metaphases analyzed (see Table 1). A secondary constriction was usually observed on its short arm, and was clearly visible in prophase stages. According to the
KUBIEI(I A N D K L E C Z K O W S K A
40
Table 1 Cytogenetic survey of the family S Percentage of metaphases with structural chromosome variant 17ph+
Patient
Number of cultures
Number of metaphases analyzed
Father
1
100
Mother
2
125
62.4
46,XX,17ph +
Son
2
132
40.9
46,XY,17ph+
Daughter
1
100
-
E
-E
16-15
16-lE
E
Karyotype
46,XX
16-18
E
16-1 8
E
16-18
E
16-1
--E
16-1 8
(i li II) E
E
E
16-12
lb-iO
16-18
Flg. 1. Partial karyotype of son (routine Giemsa staining). Note a structural chromosome variant in the 17th pair.
I .
8
Flg. 2. Giemsa banding pattern in a partial karyotype of mother. Note the same structural chromosome variant in the 17th pair as in Figure 1.
FAMI LIAL OCC UR R ENCE 0F
C H ROMO S O M E V A R I A N T 17ph +
Paris Conference (1971), this chromosome was described as a structural variant 17ph+ (Figs. 1 and 2 ) . This chromosome variant persisted in repeated lymphocyte cultures from the peripheral blood of mother and son, while simultaneously performed control cultures did not reveal similar changes.
Discussion
The structural change in the short arm of chromosome No. 17 has been interpreted by some authors as being due to satellites o n this chromosome (Berg et al. 1969, Daly 1970, Battaglia et al. 1971), while others have considered it t o be a secondary constriction (Sandstrom & Jenkins 1973, 1974). Our observations led us to the conclusion that it is a secondary constriction 17ph+, as this chromosome showed no tendency to association with satellited chromosomes of D and G groups. The structural chromosome variant 17ph+, as it appeared in the family investigated, was inherited heterozygotically from mother to son without phenotypic features. Berg et al. (1969) stressed the absence of phenotypic features connected with the homozygotic inheritance of the 17p variant. However, one of the members of the family described by these authors, in whom the heterozygotic variant 1 7 p was found, had Klinefelter syndrome. Minor structural changes in chromosomes, e.g. variants such as enlarged satellites, duplication of satellites and uncoiled chromosomes, are regarded as a population variable (Bochkov et al. 1974, Hamerton et al. 1975, Miiller et al. 1975). Nevertheless, these structural variants have also been described as having causal connection with congenital defects (Daly 1970, Palmer & Schroder 1971, Kleczkowska & Kubien 1974). So far, our previous and also our
41
present observations incline us t o the opinion that in patients with minor structural changes of chromosomes there may be a predisposition to congenital defects.
References
Battaglia, E., G. Guanti, P. Barsanti & P. Petrinelli (1971). Chromosomal survey in 298 normal subjects and 1,253 cases of congenital disorders during 1966-1970. Acta Genet. med. (Roma) 20, 123-173.
Berg, J. M., J. A. Faunch, J. M. Pendrey, L. S. Penrose, M. A. C. Ridler & A. Shapiro (1969). A homozygous chromosomal variant. Lancet i, 531. Bochkov, N. P., N. P. Kuleshov, A. N. Chebotarev, V. I. Alekhin & S. A. Midian (1974). Population cytogenetic investigation of newborns in Moscow. Hum. Genet. 22, 139-152. Daly, R. F. (1970). Chromosome aberrations in 50 patients with idiopathic mental retardation and in 50 control subjects. J . Pediat. 77, 444453.
Hamerton, J. L., N. Canning, M. Ray & S. Smith (1975). A cytogenetic survey of 14,069 newborn infants. I. Incidence of chromosome abnormalities. Clin. Genet. 8, 223-243. Kleczkowska, A. & E. Kubieli (1974). Cytogenetic studies in congenital malformations. Congenital Malformations in Krakdw Region. Part 11. Project SRS-Pol-17-69 subventioned
according to the Polish-American Memorandum of Understanding, RSW “Prasa-KsiqzkaRuch” Ed., Krakow, pp. 23-44. Littlefield, L. G., W. S. Smith, D. A. Welter & A. J. Gatz (1966). Case study of a mentally retarded female exhibiting satellites on one No. 18 chromosome. Amer. J . Obstet. Gynec. 95, 1160-1162.
Miiller, H., P. H. Klinger & M. Glasser (1975). Chromosome polymorphism in a human newborn population. Cytogenet. Cell Genet. 15, 239-255.
Nielsen. 1. R: I. Sillesen (1975). Incidence of chromosome aberrations among 11,148 newborn children. Hum. Genet. 30, 1-12. Palmer, C. G. & J . Schroder (1971). A familial variant of chromosome 9. J . med. Genet. 8, 202-208.
Paris Conference (1971). Standardization in human cytogenetics. Birth Defects: Original Article Series VIII, No. 7 .
42
KUBIEI(I A N D K L E C Z K O W S K A
Sandstrom, M. McH. & E. C. Jenkins (1973). A 17p marker chromosome familial study. Ann. Genet. 16, 267-269. Sandstrom, M. McH. & E. C. Jenkins (1974). Cytological elucidation of a 17p marker chromosome. Curyologia 21, 307-313. Schnedl, W. (1971). Banding pattern of human chromosomes. Nature new Biol. 233, 93-94.
Address: Elibieta Kuhieh, Ph.D. Cytogenetic Laboratory Department of Clinical Biochemistry Institute of Pediatrics Medical Acudemy Wielicka St. 265 30-663 Krakdw, Poland
