Pericentric Inversion Of Chromosome Research Articles

Unrelated patients with a rearrangement of chromosome 2 causing duplication of 2p23 and deletion of 2q37

We describe two unrelated patients who each have a similar chromosome 2 with duplication of 2p23 to pter, and deletion of 2q37 to qter. In one, the abnormality was derived from his mother with a pericentric inversion. Both individuals have frontal bossing; abnormally formed, low set and posteriorly rotated ears; redundant nuchal skin; inversion of the nipple(s); fleshy fingertips with prominent pads; a sacral dimple; significant developmental delay/mental retardation; and G-tube dependency. Most of these features are present in previously described individuals with either duplication of the 2p terminus or deletion of the 2q terminus. This report is the first that documents postnatal viability of individuals with concurrent duplication of 2p and deletion of 2q, and also generation of this imbalance through rearrangement of a maternally inherited pericentrically inverted 2. This report should be considered in the reproductive counseling of individuals with pericentric inversions of chromosome 2.

Pericentric inversion of chromosome 2 and echogenic vasculature in the basal ganglia: A new finding?

Linear branching echogenicities in the thalamus or basal ganglia have been reported in infants with several genetic and nongenetic disorders. In this article, we report 2 cases of newborns with a neurosonographic diagnosis of thalamic/basal ganglia vasculopathy and karyotype analysis showing pericentric inversion of chromosome 2. To our knowledge, there has been no previous mention of an association between these entities.

O▪82 PGD-PCR for a pericentric inversion of chromosome X associated with mental retardation in a man

O▪82 PGD-PCR for a pericentric inversion of chromosome X associated with mental retardation in a man

A novel pericentric inversion of chromosome 14 involving the rRNA gene cluster

A novel pericentric inversion of chromosome 14 involving the rRNA gene cluster

Beckwith?Wiedemann syndrome due to 11p15.5 paternal duplication associated with Klinefelter syndrome and a ?de novo? pericentric inversion of chromosome Y

We report on an infant who had been prenatally diagnosed with Klinefelter syndrome associated with a de novo pericentric inversion of the Y chromosome. A re-evaluation at 3 years of age suggested that he was also affected by Beckwith-Wiedemann syndrome (BWS). Karyotype was repeated and fluorescence in situ hybridisation (FISH) analysis revealed trisomy for 11p15.5-->11pter and a distal monosomy 18q (18q23-->qter). Parental cytogenetic studies showed that the father carried a balanced cryptic translocation between chromosomes 11p and 18q. Furthermore, the child had an extra X chromosome and a de novo structural abnormality of chromosome Y. Thus, his karyotype was 47,XX, inv (Y) (p11.2 q11.23), der(18) t (11;18) (p15.5;q23) pat. ish der(18) (D11S2071+, D18S1390-). Two markers on the X chromosome showed that the extra X of the child was paternally inherited. No deletions were observed on the structurally abnormal Y chromosome from any of the microsatellites studied. Clinical findings of patients with BWS due to partial trisomy 11p reveal that there is a distinct pattern of dysmorphic features associated with an increased incidence of mental retardation when comparing patients with normal chromosomes. This fact reinforces that FISH study have to be performed in all BWS patients, specially in those with mental retardation since small rearrangements cannot be detected by conventional cytogenetic techniques.

Le caryotype systématique chez les donneurs et donneuses de gamètes : utilité réelle ou simple sécurité ?

The Commission de génétique de la Fédération française des CECOS has recently sent a questionnaire to each CECOS asking for the year of activity starting, the number of karyotypes performed every year, the number and the type of chromosomal abnormalities and the consequences for the donation process. For sperm donors, 9410 karyotypes have been realized during a mean number of 21.3 years. Fifty-seven chromosomal abnormalities (0.6%) have led to the exclusion of the donors, twenty of which being directly dangerous for the offspring [eight t(13;14), three reciprocal translocations, two structural abnormalities of unknown origin and seven inversions]. Twenty-three anomalies (three supernumerary markers, five 47,XYY, five fragile sites and ten mosaicism) as well as nine other (three Y chromosome inversions and six pericentric inversions of chromosome 9), although considered either as innocuous or as chromosomal variants, have also been excluded. Lastly, five miscellaneous abnormalities have also been considered as exclusion factors. Familial data and sperm counts were known for 28 of these donors. For egg donors, only 681 karyotypes have been performed during a mean number of 7.8 years of activity. Five karyotype abnormalities have led to the exclusion of the donor: one 47,XXX , one mosaicism 45,X/47,XXX/46,XX , one case of non specific rearrangements in half of mitosis and two reciprocal translocations [t(8;20) (q13;p13) et t(3;17) (q26;p13)]. The consequences of this study on gamete donor genetic screening are discussed.

Cloning of the breakpoints of a de novo inversion of chromosome 8, inv (8)(p11.2q23.1) in a patient with Ambras syndrome

Ambras syndrome (AMS) is a unique form of universal congenital hypertrichosis. In patients with this syndrome, the whole body is covered with fine long hair, except for areas where normally no hair grows. There is accompanying facial dysmorphism and teeth abnormalities, including retarded first and second dentition and absence of teeth. In 1993, Baumeister et al. reported an isolated case of Ambras syndrome in association with a pericentric inversion of chromosome 8. Subsequently, another patient with congenital hypertrichosis and rearrangement of chromosome 8 was reported by Balducci et al. (1998). Both of these patients have a breakpoint in 8q22 in common suggesting that this region of chromosome 8 contains a gene involved in regulation of hair growth. In order to precisely determine the nature of the rearrangement in the case of Ambras syndrome, we have used fluorescent in situ hybridization (FISH) analysis. We have cloned the inversion breakpoints in this patient and generated a detailed physical map of the inversion breakpoint interval. Analysis of the transcripts that map in the vicinity of the breakpoints revealed that the inversion does not disrupt a gene, and suggests that the phenotype is caused by a position effect.

SNTG1, the gene encoding gamma1-syntrophin: a candidate gene for idiopathic scoliosis.

Idiopathic scoliosis (IS) affects approximately 2%-3% of the population and has a heritable component. The genetics of this disorder are complex. Here, we describe a family in which a pericentric inversion of chromosome 8 co-segregates with IS. We have used fluorescence in situ hybridization to identify cloned DNAs that span the breakpoints on the two arms of the chromosome. We have identified a bacterial artificial chromosome (BAC) of 150 kb that crosses the q-arm breakpoint and a BAC of 120 kb that crosses the p-arm breakpoint. The complete genomic DNA sequence of these BACs has been analyzed to identify candidate genes and to localize further the precise breakpoints. This has revealed that the p-arm break does not interrupt any known gene and occurs in a region of highly repetitive sequence elements. On the q-arm, the break occurs between exons 10 and 11 of the gamma-1 syntrophin (SNTG1) gene. Syntrophins are a group of cytoplasmic peripheral membrane proteins that associate directly with dystrophin, the Duchenne muscular dystrophy gene; gamma1-syntrophin has been shown to be a neuronal cell-specific protein. Mutational analysis of SNTG1 exons in 152 sporadic IS patients has revealed a 6-bp deletion in exon 10 of SNTG1 in one patient and a 2-bp insertion/deletion mutation occurring in a polypyrimidine tract of intronic sequence 20 bases upstream of the SNTG1 exon 5 splice site in two patients. These changes were not seen in a screen of 480 control chromosomes. Genomic DNAs from seven affected individuals within the family of a patient carrying the 6-bp deletion were typed to determine whether the alteration co-segregated with IS. The deletion was only observed in five out of these seven individuals. Thus, although genetic heterogeneity or multiple alleles cannot be ruled out, the 6-bp deletion does not consistently co-segregate with the disease in this family.

A familial complex chromosome translocation resulting in duplication of 6p25

We report on a girl with psychomotor retardation, severe speech developmental delay and mild dysmorphic features. Molecular cytogenetic analysis showed that the patient was carrier of an insertion (6)(p22.5→22.4) in chromosome 12. Analysis of the chromosomes of the mother revealed the presence of a complex chromosomal rearrangement. In addition to the insertion (6)(p22.5→22.4) in chromosome 12 and a pericentric inversion in chromosome 12, the 6p subtelomeric region was absent in the mother. This is, to our knowledge, the smallest pure duplication of chromosome 6p as well as the smallest cryptic subtelomeric 6pter deletion thus far reported.

Chromosomal rearrangements in cattle and pigs revealed by chromosome microdissection and chromosome painting.

A pericentric inversion of chromosome 4 in a boar, as well as a case of (2q-;5p+) translocation mosaicism in a bull were analysed by chromosome painting using probes generated by conventional microdissection. For the porcine inversion, probes specific for p arms and q arms were produced and hybridised simultaneously on metaphases of a heterozygote carrier. In the case of the bovine translocation, two whole chromosome probes (chromosome 5, and derived chromosome 5) were elaborated and hybridised independently on chromosomal preparations of the bull who was a carrier of the mosaic translocation. The impossibility of differentiating chromosomes 2 and der(2) from other chromosomes of the metaphases did not allow the production of painting probes for these chromosomes. For all experiments, the quality of painting was comparable to that usually observed with probes obtained from flow-sorted chromosomes. The results obtained allowed confirmation of the interpretations proposed with G-banding karyotype analyses. In the bovine case, however, the reciprocity of the translocation could not be proven. The results presented in this paper show the usefulness of the microdissection technique for characterising chromosomal rearrangements in species for which commercial probes are not available. They also confirmed that the main limiting factor of the technique is the quality of the chromosomal preparations, which does not allow the identification of target chromosomes or chromosome fragments in all cases.

Abnormal constitutional karyotypes in patients with neuroblastoma: a report of four new cases and review of 47 others in the literature

Anomalies of constitutional karyotype, which have led to the discovery of oncogenes and tumor-suppressor genes in embryonal tumors such as retinoblastoma and Wilms tumor, have, until recently, rarely been reported until recently in neuroblastoma. We present four new cases of neuroblastoma associated with (a) a mosaicism for monosomy 22; (b) an 11q interstitial deletion; (c) a pericentric inversion of chromosome 9 at band 9p21; and (d) a Robertsonian translocation t(13;14). These anomalies and 47 others in the literature are worthy of interest, because some are recurrent, involving the same chromosome regions (1p36, 2p23, 3q, 11q23, and 15q), and some anomalies are situated on chromosome regions known to contain genes involved in neuroblastoma development (1p, 2p, 9p, 11q, 16q, and 17q). Chromosome regions 3q and 15q, observed several times, may also contain genes significant for neuroblastoma onset or development. Furthermore, the lack of neuroblastoma in patients with Down syndrome and Klinefelter or triple-X syndromes, together with a probable excess of neuroblastoma in patients with Turner syndrome, suggests that genes of importance for neuroblastoma may map to chromosomes X and 21. A search for genes implicated in neuroblastoma biology should use these data.

Disruption of a novel member of a sodium/hydrogen exchanger family and DOCK3 is associated with an attention deficit hyperactivity disorder-like phenotype

Background: Attention deficit hyperactivity disorder (ADHD) is a complex condition with high heritability. However, both biochemical investigations and association and linkage studies have failed to define fully the underlying genetic...

Interictal Schizophrenia-like Psychosis in a Patient With Double Cortex Syndrome

The authors report a female patient with sporadic double cortex syndrome who manifested recurrent interictal schizophrenia-like psychoses. She had no mutations in the doublecortin gene but a pericentric inversion of chromosome 9. Neurodevelopmental disturbances and seizures may be associated with her mental dysfunction.

Interictal Schizophrenia-like Psychosis in a Patient With Double Cortex Syndrome

The authors report a female patient with sporadic double cortex syndrome who manifested recurrent interictal schizophrenia-like psychoses. She had no mutations in the doublecortin gene but a pericentric inversion of chromosome 9. Neurodevelopmental disturbances and seizures may be associated with her mental dysfunction.

ALLOGENEIC MARROW GRAFTS FROM UNRELATED DONORS WITH CONGENITAL PERICENTRIC INVERSION OF CHROMOSOME 9

Allogeneic marrow transplantation from related donors with congenital chromosomal abnormalities has been reported (Barquinero et al, 1995). A higher incidence of graft failure was encountered in Down's syndrome and Fanconi syndrome heterozygotes. We describe two cases of allogeneic bone marrow transplantation from unrelated donors with pericentric inversion of chromosome 9. Case 1. A 44-year-old woman underwent allogeneic bone marrow transplantation for chronic myeloid leukaemia in myeloblastic crisis from a human leucocyte antigen (HLA)-matched unrelated male donor, after high-dose cyclophosphamide and fractionated total body irradiation, in 1993. She received non-manipulated bone marrow with a total of 2·1 × 108 mononuclear cells/kg. Myeloid engraftment was attained by d +24. However, she continued to have poor erythroid and platelet recovery requiring frequent transfusions. Two months after transplant, her white blood cell (WBC) count decreased to 1·3 × 109/l and the platelet count to 10 × 109/l. Repeat bone marrow examination revealed hypocellular marrow consistent with graft failure. Cytogenetic studies of the bone marrow revealed donor male phenotype of 46 XY, inv(9). Granulocyte colony-stimulating factor (G-CSF) was started and her blood counts gradually recovered 4 weeks later. The patient is alive with normal blood counts and no evidence of leukaemic recurrence, 6 years later. Case 2. A 23-year-old man, diagnosed with severe aplastic anaemia in 1989, was initially treated with antithymocyte globulin with no response. He underwent allogeneic bone marrow transplant from an HLA-matched unrelated female donor in July 1990 after conditioning with high-dose cyclophosphamide, cytarabine arabinoside (ara-C), methylprednisolone and total body irradiation. A total of 4·68 × 108 mononuclear cells/kg were harvested and T-cell depleted prior to transplantation (Hsu et al, 1987). Xomazyme, an anti-CD5-ricin A chain immunotoxin, and methylprednisolone were used for graft-versus-host disease (GVHD) prophylaxis. He developed grade II acute GVHD on d +28 that was treated successfully with a brief course of high-dose methylprednisolone. The patient had poor engraftment with WBC 1·5 × 109/l on d +56; WBC 1 × 109/l and platelets 8 × 109/l on d +75; WBC 1·9 × 109/l and platelets 10 × 109/l on d +125. Repeat bone marrow biopsy was hypocellular with overall cellularity < 10%. Cytogenetic study of the bone marrow showed 46, XX, inv(9). He received a course of antithymocyte globulin in November 1990 without response. G-CSF was started in January 1991 which resulted in a WBC increase to 11 × 109/l, a Hb level of 8·7 g/dl, and a platelet level of12 × 109/l. Unfortunately, the patient developed cytomegalovirus pneumonia and retinitis. Two months later, the patient succumbed shortly after diagnosis from post-transplant high-grade immunoblastic lymphoma in the brain. In recent years, the incidence of constitutional chromosomal abnormalities in apparently normal individuals has increased. Pericentric inversion of chromosome 9 occurs in about 1–1·5% of the normal population (Tawn & Earl, 1992; Lamb et al, 1994). Although it is generally regarded as a normal variant, it has been implicated in infertility, recurrent abortion and psychiatric disorders (Uehara et al, 1992; Daya, 1994; Inayama et al, 1997). Despite theprevalent occurrence, there has not been any report of bone marrow transplantation involving these individuals either as a donor or recipient. To our knowledge, this is the first report of allogeneic bone marrow transplantation from donors with constitutional inv(9). Persistent cytopenia after bone marrow transplantation is common and may be as a result of a variety of causes, such as inadequate stem cell dosage, purging, graft rejection, antibiotics, intercurrent viral infection, etc. It is conceivable that graft failure of these two cases is simply coincidental. Alternatively, it is possible that donor marrow with constitutional inv(9) may be associated with delayed haematopoietic recovery, which has also been described in allografts from donors with Down's syndrome and Fanconi anaemia heterozygotes (Barquinero et al, 1995). Further studies and case reporting are required to confirm our observation.

Karyotype analysis of 161 unrelated schizophrenics: no increased rates of X chromosome mosaicism or inv(9), using ethnically matched and age-stratified controls

Chromosomal aberrations have long been studied in an effort to identify susceptibility genes in schizophrenia. The two most frequently detected abnormalities are X chromosome mosaicism in female patients and pericentric inversions of chromosome 9 [inv(9)]. Chromosome X aneuploidies are known to be age dependent but differences due to ethnicity remain undetermined. In the case of inv(9), its prevalence in the general population varies with ethnicity. To evaluate the importance of these karyotypic changes in schizophrenia, cytogenetic analysis was performed on 161 unrelated schizophrenics of Japanese origin. We observed an increase in the incidence of X chromosome mosaicism in female schizophrenics with age. However, when compared with age matched female controls (92 individuals), no significant differences between patient and control samples were detected. Moreover, this study showed that there is no significant difference in the incidence of X chromosome loss between Japanese and Caucasian populations. The four cases with inv(9) (2.5%) detected in this study, did not differ significantly from the reported incidence of between 1.7 and 2.1% seen in the general Japanese population. We also observed a small number of additional karyotypic changes, none of which were recurrent. This is the first report to examine the comparative rates of X mosaicism in female schizophrenics and age matched controls.

Pericentric inversion in natural populations of Oligoryzomys nigripes (Rodentia: Sigmodontinae).

We analysed polymorphism for pericentric inversion in chromosome 3 of Oligoryzomys nigripes (Rodentia: Sigmodontinae) in several populations in Brazil and examined the meiotic behaviour of this chromosome in heterozygotes. We observed an orderly pairing of all chromosomes at pachytene in heterozygotes for the inverted chromosome 3. No indication of meiotic arrest and germ-cell death was found. Electron microscopy of synaptonemal complexes and conventional meiotic analysis indicated strictly nonhomologous synapsis and crossing-over suppression in the inverted region in the heterozygotes, which prevent the formation of unbalanced gametes. Thus, the pericentric inversion in chromosome 3 does not apparently result in any selective disadvantages in heterozygous carriers. In the majority of the populations studied, the frequencies of acrocentric homozygotes, metacentric homozygotes, and heterozygotes were in Hardy-Weinberg equilibrium. However, in some populations, we detected an excess of heterozygotes and a deficiency of acrocentric homozygotes.

A Down syndrome case with a karyotype of 46,XY,rec(21)dup(21q)inv(21)(p11q22) derived from paternal pericentric inversion of chromosome 21

A Down syndrome case with a karyotype of 46,XY,rec(21)dup(21q)inv(21)(p11q22) derived from paternal pericentric inversion of chromosome 21

Prenatal diagnosis of translocation and a single pericentric inversion 9: the value of fetal ultrasound

A total of 2741 high-risk pregnant mothers underwent invasive prenatal procedures, and in 94 of them (3·4%), fetal chromosomal or genetic anomalies were detected. In this study, we report on single pericentric inversions of chromosome 9 as well as translocations, which constituted 32% (30 of 94) and 16% (15 of 94) of all identified chromosomal or genetic abnormalities, respectively. In six fetuses of the 30 with an inversion of chromosome 9, ultrasound findings were abnormal and consisted of hydramnios, anhydramnios, hydroureter, hydronephrosis, encephalocele and prune belly syndrome, occurring singly or in combination. Among the 15 fetuses with chromosomal translocations, five had sonographic abnormalities. In conclusion, we found detailed ultrasound survey of fetuses with either translocations or inversions of chromosome 9 to be an additional source of useful information concerning fetal status that could be of value in genetic counselling of affected parents.

A new recessive ametapodia mutation in the chicken (Gallus domesticus).

An apparently new mutation that is associated with abnormal limb development appeared in a strain of Light Brown Leghorn chickens. Mutants are characterized by the complete absence of the tarsometatarsals, while severely hypoplastic development of the metacarpals is also present. The phenotype of the new mutant (ametapodia-2) closely resembles ametapodia-1, described in 1967, but ametapodia-2 is inherited as an autosomal recessive (AMET*A), while ametapodia-1 was associated with an incompletely dominant gene (MP*A). Only heterozygous ametapodia-1 (MP*N/MP*A) were viable and able to reproduce, while homozygous ametapodia-2 mutants do not normally survive beyond 2-4 days of age. The shankless mutation (SHL*S) also reduces development of the metatarsal and metacarpal bones and has been shown to be associated with a pericentric inversion of chromosome 2. No obvious cytologic abnormality was apparent in ametapodia-2 birds, and offspring of a cross between AMET*A carriers and shankless birds were normal, indicating that the two mutations are not alleles. Ametapodia-1 (MP*A) was found to be linked to the rose comb locus (R) by 16 crossover units. Linkage test matings between AMET*A and (R*R) showed independent segregation, strongly suggesting that the mutation occurred at a relatively distant locus and therefore is probably not allelic to MP*A.