J Med Genet: first published as 10.1136/jmg.18.1.54 on 1 February 1981. Downloaded from Joutrnal ofMedical Genetics, 1981, 18, 54-58 Homodicentric chromosomes: a distinctive type of dicentric chromosome * BRIAN E WARD, CYNTHIA M BRADLEY, JANE B COOPER, AND ARTHUR ROBINSON From the National Jewish Hospital and Research Center/National Asthma Center; and Department ofBiophysics and Genetics ofthe University ofColorado School ofMedicine, Denver, Colorado, USA. SUMMARY This report describes two patients with a distinctive type of dicentric autosomal chromo- some formed by breakage and union between homologous chromosomes. These stable chromosomes possess two C bands, implying the presence of two centromeric regions. The first child, evaluated for dysmorphic features, was shown to have an abnormal chromosome 16, designated as 46,XX, -16,+dic(16)(pter-*cen-*q22::pll-*qter). The second case is a child with the typical features of trisomy 18 whose karyotype is designated as 46,XX,-18,+dic(18)(qter-*pl l1: :pl l 3--cen-*qter). The stability of these chromosomes is presumably the result of centromere suppression and associated premature centromere division of the suppressed centromere. The possible mechanism of formation of these homodicentric chromosomes is presented, and a comparison is made between them and three patients with dicentric X chromosomes. The identification of stable dicentric chromosomes samples were stained using GTG,7 CBG,8 and has been simplified by the use of C banding. Struc- QFQ9 banding. turally abnormal sex chromosomes, as well as Robertsonian translocations, often possess two C Case reports http://jmg.bmj.com/ bands, implying the presence of two centromeric regions.1-3 Case 1 was the female offspring of an uncomplicated This report describes two cases representing a new term pregnancy. At birth, height and head circum- type of dicentric chromosome with two C band ference were at the 50th centile while weight was regions formed by meiotic breakage and subsequent below the 3rd centile. Birth asphyxia and meconium joining between homologous chromosomes. These aspiration were present. Evaluation at 10 months of homodicentrics will be compared to the three types age revealed the following abnormalities: head cir- cumference and weight below the 3rd centile, of structurally abnormal X chromosomes proposed on October 2, 2021 by guest. Protected copyright. by Hsu et al: an isochromosome, an isodicentric hypotonia, right facial hemihypertrophy, persistent isochromosome X with two C band regions (type 1), ductus arteriosus, bilateral transpalmar creases, and an asymmetrical isodicentric X chromosome abnormal gross motor movements, and develop- with two C band regions (type 2). mental delay. Case 2 was the female offspring of an 8 month gestation. At birth numerous congenital abnor- Methods malities were present, including epicanthic folds, bilateral cleft lip, redundant skin around the neck, Peripheral lymphocyte cultures were established and absent right clavicle, rib abnormalities, and rocker- harvested in the usual fashion.45 Fibroblast cultures bottom feet. The patient died at 6 weeks of age with were also established on one patient (case 2).6 All the clinical diagnosis of trisomy 18. Blood and tissue samples were obtained upon death. *This work was supported in part by grants from The Case 3 was referred at the age of 20 years with a Genetic Foundation, Inc, The Boettcher Foundation, and history of primary amenorrhoea, short stature The Henry J Kaiser Family Foundation. (145 cm), cubitus valgus, immature genitalia, and Received for publication 10 March 1980 short fourth metacarpals. 54 J Med Genet: first published as 10.1136/jmg.18.1.54 on 1 February 1981. Downloaded from Homodicentric chromosomes: a distinctive type of dicentric chromosome 55 .- * ' g 7 g $6 + - -7 ma~ ~ ~ FIG 1 Homodicentric chromosomes andpresumedmechanism offormation. (A) case 1; (B) case 2. - . I.- :. ..1. "' -t;m- b. .'- -- - --b- -- e -. e -. ..c .D.- 4 ,- t- ". im - - -- - I soc h romc some X(X)c http://jmg.bmj.com/ 1 4 C.B ) o-c_Verf on October 2, 2021 by guest. Protected copyright. B X. c (X)qterX -* D -*;Pqter %i isodicentrc crromrcsore type2, 4 C 46.X ,c X?(qter-4cen--z2, p21-qter ) FIG 2 Structurally abnormal X chromosomes. (A) case 3; (B) case 4; (C) case 5. J Med Genet: first published as 10.1136/jmg.18.1.54 on 1 February 1981. Downloaded from 56 Brian E Ward, Cynthia M Bradley, Jane B Cooper, and Arthur Robinson Case 4 was referred at the age of 20 with a history Discussion of primary amenorrhoea and short stature (145 cm). Secondary sexual characteristics developed normally Homodicentric chromosomes represent a distinctive beginning at the age of 10. type of chromosomal aberration described here for Case 5 was evaluated at 14 years of age for the first time in autosomes. The mechanism of delayed puberty, short stature, slight webbing of the homodicentric chromosome formation may best be neck, and bilateral deafness. understood by comparison with other types of di- centric chromosomes (fig 3). Cytogenetic results The most common type of dicentric autosomal chromosome is derived from a Robertsonian trans- HOMODICENTRIC CHROMOSOMES (FIG 1) location.2 Most Robertsonian translocations can be Case 1. Cytogenetic analysis revealed the presence interpreted as stable dicentrics possessing one of a structurally abnormal chromosome in all meta- functional centromere and two C band regions. The phases analysed. The G banding pattern was most consistent with a structurally abnormal chromosome Dicentric 16. This chromosome had two C band regions and chromosomes was interpreted as being a stable dicentric chromo- Resulting from Robertsonian translocat ions some formed by breakage and union of two homo- logous chromosomes. The karyotype is designated as 46,XX, -16, +dic(16)(pter-*cen-*q22: :pl 1-*qter). lo + ,_, The patient is then trisomic for a portion of the short arm and long arm of chromosome 16 (pll> q22). Parental chromosomes were normal. Resulting from non-Robertsonian translocations Case 2. The presence of an abnormal chromosome 18 was noted on initial G band analysis. Two C band regions were present in the abnormal 18 in all lymphocyte and fibroblastic cells analysed. The interpretation of this dicentric is designated as + 46, XX,-1 8, + dic (I8) (qter*ppI I -lI: : plI I* 3-cen-- qter). The patient is then trisomic for the long arm and a portion of the short arm of chromosome I sochromosomes 18 (p1I 1-*lqter) and monosomic for a small segment http://jmg.bmj.com/ of the short arm (p1Il 3-*pter). Maternal chromo- somes were normal. Li7 + STRUCTURALLY ABNORMAL X CHROMOSOMES (FIG 2) Isodicentric chromosomes Case 3. The presence of an isochromosome X with a single C band was observed. The karyotype is on October 2, 2021 by guest. Protected copyright. designated as 46,X,i(X)(qter-*cen-*qter). Case 4. Three cell lines were present in the patient. An isodicentric X chromosome was present in two cell lines. This isodicentric X chromosome had two C band regions and is identical to the type 1 isodi- centric chromosome of Hsu et al.1 The karyotype is designated 45,X/46,X,dic(X)(qter->pl ::rl!-4 qtcr)/ 47,X,dic(X),dic(X). The proportion of cell types Homodicentric chromosomes present was 3 - 3 %, 92- 3 %, and 3 - 3 %, respectively. Case 5. Two cell lines were detected in this patient: 45,X/46,X,dic(X)(qter->cen- p21 : :p21-qter). The P abnormal X was observed in 93 % of cells. Two C band regions were present in the abnormal X chromo- some. Because of the presence of asymmetry Point of breakage (~ between the two arms, this would be consistent with FIG 3 Mechanisms offormation ofdicentric chromo- the type 2 isodicentric chromosome of Hsu et a1.l somes. J Med Genet: first published as 10.1136/jmg.18.1.54 on 1 February 1981. Downloaded from Homodicentric chromosomes: a distinctive type ofdicentric chromosome 57 stability is thought to result from centromere blasts of case 2. The absence of mosaicism is con- suppression and associated premature division of sistent with a meiotic recombination event followed the suppressed centromere.2 by centromere suppression and premature centro- Non-Robertsonian translocations involving auto- mere division (fig 1), preventing the formation of somes have been reported to form dicentric chromo- an anaphase bridge on first centromere division. somes.1'-'2 Breaks in non-homologous chromo- The observed banding patterns are most consistent somes are followed by fusion. The appearance of with homologous chromosome union rather than these dicentric chromosomes may vary in different recombination within a single chromosome, as metaphases from the same sample. When two illustrated by the homodicentric chromosome 16 primary constrictions are observed the dicentric is (case 1) where the banding pattern reveals that unstable, and, as a result, is present only in a pro- portions of two chromosomes 16 are joined to each portion of cells. If, however, there is only one other in the same orientation. If this abnormal primary constriction, there is centromere suppression chromosome had arisen from a crossover in an and presumptive premature centromere division of inversion loop or sister chromatid union, one one centromere, and the dicentric then behaves as a would expect the long arms of the chromosome 16 stable monocentric chromosome.13 The above to be in opposite orientation, similar to that ob- chromosomes are 'heterodicentric' involving centro- served in isodicentric X chromosomes. Wisniewski meres derived from two non-homologous chromo- et al15 have described an abnormal dicentric chromo- somes. some 9 presumably derived from union of homo- An isochromosome is usually formed by mis- logous chromosomes. One of the chromosomes 9 division of the centromere, leading to the formation had a large qh region and the resulting abnormal of two metacentric chromosomes in which one arm is chromosome had two distinctively different types of the mirror image of the other.