Horacio Rivera

Molecular cytogenetic analysis of eight inversion duplications of human chromosome 13q that each contain a neocentromere.

Neocentromeres are fully functional centromeres that have arisen in previously noncentromeric chromosomal locations on rearranged chromosomes. The formation of neocentromeres results in the mitotic stability of chromosomal fragments that do not contain endogenous centromeres and that would normally be lost. Here we describe a unique collection of eight independent patient-derived cell lines, each of which contains a neocentromere on a supernumerary inversion duplication of a portion of human chromosome 13q. Findings in these patients reveal insight into the clinical manifestations associated with polysomy for portions of chromosome 13q. The results of FISH and immunofluorescent analysis of the neocentromeres in these chromosomes confirm the lack of alpha-satellite DNA and the presence of CENtromere proteins (CENP)-C, -E, and hMAD2. The positions of the inversion breakpoints in these chromosomes have been placed onto the physical map of chromosome 13, by means of FISH mapping with cosmid probes. These cell lines define, within chromosome 13q, at least three distinct locations where neocentromeres have formed, with five independent neocentromeres in band 13q32, two in band 13q21, and one in band 13q31. The results of examination of the set of 40 neocentromere-containing chromosomes that have thus far been described, including the 8 neocentromere-containing chromosomes from chromosome 13q that are described in the present study, suggest that chromosome 13q has an increased propensity for neocentromere formation, relative to some other human chromosomes. These neocentromeres will provide the means for testing hypotheses about sequence requirements for human centromere formation.

FISH and molecular study of autosomal supernumerary marker chromosomes excluding those derived from chromosomes 15 and 22: I. Results of 26 new cases

The chromosomal origins and in some cases the molecular composition of 26 autosomal supernumerary marker chromosomes (SMC) were identified using combined fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) techniques. Fifteen were de novo, 4 maternally and 2 paternally transmitted and in 5 cases the parental origin is not known. Eleven cases were non-mosaic and fifteen cases had SMC cell lines ranging from 8-87%. Ten cases were ascertained prenatally, nine postnatally with abnormal phenotypes, three with poor reproductive histories and four co-incidentally. Five SMC were small rings from chromosomes 3, 6 (2 cases), 20 and 21; 8 were bisatellited from chromosomes 13/21 (4 cases), 14 (3 cases) and 14/22 (1 case). The remaining 13 appeared to be minutes comprising centromeric material only from chromosomes 1, 4, 12, 13/21 (2 cases), 14 (3 cases), 16 (2 cases), 19; 5/19, and a centric fusion involving 13 or 21 and 14. Euchromatin was detected in 9 out of 18 SMC tested with paints and/or PCR, and abnormal phenotypes were most commonly observed in patients with small ring shaped SMCs containing euchromatic sequences. Uniparental paternal isodisomy (UPD) for chromosome 6 was detected in one patient but was the only example of UPD for the normal homologues in association with an autosomal SMC in an overall total of 30 cases examined.

Peutz‐Jeghers syndrome with feminizing sertoli cell tumor

A case involving a 6‐year‐old boy with Peutz‐Jeghers syndrome and an unilateral feminizing Sertoli cell tumor is described. Endocrinologic studies revealed consistently high plasma and urine levels of estrogens and normal levels of testosterone and dihydrotestosterone. The increased levels of estrogens did not show changes that could be correlated with exogenous gonadotropin administration, thus indicating an autonomous nature. The histopathologic studies of nontumorous testicular tissue revealed changes in the seminiferous tubules which suggested that estrogens, directly or indirectly, may have had both stimulating and atrophying effects. It is concluded that gonadal tumors are an additional manifestation of the Peutz‐Jeghers syndrome gene in both male and female patients. Cancer 46:223–228, 1980.

Severe Silver‐Russell syndrome and translocation (17;20) (q25;q13)

Ramírez‐Dueñas ML, Medina C, Ocampo‐Campos R, Rivera H. Severe Silver‐Russell syndrome and translocation (17;20)(q25;q13). Clin Genet 1992:41: 51–53.

Retinoblastoma-del(13q14): Report of two patients, one with a trisomic sib due to maternal insertion. Gene-dosage effect for esterase D

SummaryTwo cases of del(13)-retinoblastoma are reported. Case 1, a 13-month-old male, was monosomic due to the malsegregation of the maternal ins(20;13)(p12;q1307q14.3). The patients sister was trisomic for 13q1307q14.3 with no evident phenotypic effect. Case 2 was a 20-month-old female with a de novo del(13)(q1303q14.3). In both instances esterase D activity showed a remarkable gene-dosage effect in monosomy, disomy, and trisomy, thus confirming the assignment of the gene locus to 13q14, and more precisely to the proximal half of this band. In all instances, the ESTD phenotypes were 1-1. It is suggested that esterase D activity should become an important diagnostic criteria for the various etiological forms of retinoblastoma.

A new form of hypertrichosis inherited as an X-linked dominant trait.

SummaryA family with a distinct form of congenital generalized hypertrichosis was studied. Males were more severely affected than females, who exhibited asymmetric hair distribution. This finding was attributed to lyonization, since genealogical studies indicated an X-linked pattern of inheritance. A back mutation is postulated as the origin of this new phenotype.

Langer-Giedion syndrome with and without del 8q. Assignment of critical segment to 8q23

SummaryTwo patients with typical Langer-Giedion or trichorhino-phalangeal type II syndrome are reported. One had an apparently normal karyotype. The second had an intercalary del 8q23. Attention is drawn to the severe bone defects seen in the latter and observations from the literature are discussed. The critical segment is assigned to band 8q23. The syndrome may result in a number of cases from a visible deletion, and in other instances from a more conventional gene mutation, although the molecular mechanism is uncertain.

Chromosomal Abnormalities in Couples with Reproductive Disorders

Aim: To determine the prevalence of chromosomal abnormalities in couples with reproductive disorders. Methods: A retrospective study was performed in 939 Mexican couples with reproductive disorders (542 with recurrent fetal loss, 356 with malformed/stillborn children, and 41 with sterility) whose karyotype was established on GTG-banded metaphases. Results: A chromosomal aberration was detected in one partner of 52 couples, including a double translocation carrier; therefore, the prevalence of chromosomally abnormal couples was 5.5%; 31 couples with recurrent fetal loss (31/542, 5.7%), 15 with malformed/stillborn children (15/356, 4.2%), and 6 with sterility (6/41, 14.6%). There were 43 couples with structural rearrangements (29 reciprocal translocations, 10 robertsonian translocations, 2 inversions, 1 insertion, and 1 ring) and 9 with gonosomal aneuploidies. The affected partner was female in 28 (53.8%) and male in 24 (46.2%) couples. In addition, 17 couples (1.8%) with the structural variant inversion 9qh were detected. Conclusion: The prevalence of chromosomal abnormalities found in our sample is consistent with figures described in several populations around the world.

Centric fission, centromere‐telomere fusion and isochromosome formation: a possible origin of a de novo 12p trisomy

A 5‐month‐old girl had a typical 12p trisomy syndrome due to a monocentric i(12p) present in a 46‐chromosome complement that also included the translocation of all 12q onto the 8p telomere; i.e., her complex karyotype could be written as 46.XX, – 8,–12,+ der(8),t(8;12)(p23.3;cen), + i(12p). The present concurrence of a whole‐arm q translocation and an i(p) for a single chromocome, along with six previous similar instances involving chromosomes 4, 5 and 9, suggests the following origin for such a special rearrangement: a centric fission in Gl initially yielding two telocentrics; at the next replication, the tel(q) translocates onto a nonhomologous telomere (centromere‐telomere fusion), whereas the tel(p) becomes an i(p). This mechanism can be either meiotic or postzygotic and surmises that the translocated long arm retains a partial centromere, which subsequently is inactivated and loses its staining properties.

Pure monosomy and trisomy 2q24.2→q3105 due to an inv ins(7;2)(q21.2;q3105q24.2) segregating in four generations

SummaryAn inv ins(7;2)(q21.2;q3105q24.2) was found to segregate through four generations of a family. Adjacent-1 segregation aneusomies were ascertained in five patients: three monosomics and two trisomics; and the corresponding syndromes were delineated. The comparative analysis between these and other previously described 2q aneusomic individuals led to the conclusion that a large cleft between first and second toes is a constant feature in monosomy 2q24→q31. No other trait could plausible be mapped. Risks of 7.9 to 31.9% for aneusomic children and of 26.3% for abortion were estimated in the present family.