Diagnóstico prenatal de inversión pericéntrica del cromosoma cinco de novo en una paciente con gestación a término sin complicaciones posteriores / Prenatal diagnosis of pericentric de novo inversion in the fifth chromosome in a patient with term birth without posterior complications

Resumen Los avances en las técnicas de citogenética han permitido detectar con mayor precisión alteraciones cromosómicas tanto estructurales como de número. La amniocentesis genética es una prueba invasiva que se realiza entre la semana 16 y 20 de gestación que nos permite detectar distintas alteraciones cromosómicas. Presentamos un caso de una paciente que se le realizó a las 18 semanas de gestación la amniocentesis por edad materna avanzada (39 años), evidenciándose en el cariotipo una inversión pericéntrica del cromosoma 5. Se procedió a realizar cariotipos a los padres, ambos normales. De acuerdo con este resultado a la paciente se le realizó ecosonogramas para detectar si el feto presentaba malformaciones y se realizó asesoramiento genético. A continuación, se hizo evaluación del recién nacido y seguimiento durante 4 años para evaluar fenotipo y desarrollo neurológico. Como se comentará, el cromosoma 5 codifica para muchos genes y es responsable de muchas patologías, de las cuales este paciente no presentó ninguna.

Abstract Advances in cytogenetic techniques have made it possible to, more accurately, detect both structural and number chromosomal alterations. Genetic amniocentesis is an invasive test that is performed between week 16 and 20 of gestation that allows us to detect chromosomal alterations. We present a case of a patient who underwent amniocentesis by advanced maternal age (39 years) at 18 weeks of gestation, showing a pericentric inversion of chromosome 5 in the karyotype and proceeded to perform karyotypes of the parents, both normal. According to this result, the patient was screened for fetal malformations and genetic counseling. Newborn evaluation and 4-year follow-up to assess phenotype and neurological development. As discussed, chromosome 5 codes for many genes and is responsible for many pathologies that this patient did not present.

First cytogenetic record for a species of Otothyropsis Ribeiro, Carvalho & Melo, 2005 (Loricariidae, Hypoptopomatinae)

Hypoptopomatinae is a monophyletic subfamily that includes 147 species, distributed in 20 genera. Otothyropsis is a genus of Hypoptopomatinae, recently described. Here, we provided the first cytogenetic information of Otothyropsis . The specimens were collected from córrego Dourado, a small tributary of rio Iguatemi, which flows into rio Paraná. The specimens of Otothyropsis cf. polyodon were analyzed with respect to diploid number, C-Band and Ag-NOR patterns. The diploid number was 54 chromosomes, distributed in 18 metacentric, 28 submetacentric, and 8 subtelocentric chromosomes, with single Ag-NOR and conspicuous heterochromatic blocks on the short and long arms of the 24th pair of chromosomes. Our study highlights the conservation trend of the diploid number (2n=54) and fundamental number (FN = 108) among the species of Hypoptopomatinae. However, the karyotype formula (18m+28sm+8st) seems to be specific to O. cf. polyodon , considering the other Hypoptopomatinae species already analyzed.

Hypoptopomatinae é uma subfamília monofilética que inclui 147 espécies distribuídas em 20 gêneros, sendo Otothyropsis um gênero recentemente descrito. Aqui, fornecemos a primeira informação citogenética do gênero Otothyropsis . Espécimes foram coletados no córrego Dourado, um pequeno tributário do rio Iguatemi, o qual deságua no rio Paraná. Espécimes de Otothyropsis cf. polyodon foram analisados em relação ao número diploide e padrões de Banda-C e Ag-NOR. O número diploide foi de 54 cromossomos, distribuídos em 18 metacêntricos, 28 submetacêntricos e 8 subtelocêntricos, com Ag-NOR simples e blocos heterocromáticos evidentes no braços curto e longo do par de cromossomos 24. Nosso estudo destaca a tendência de conservação do número diploide (2n=54) e número fundamental (NF=108) entre as espécies de Hypoptopomatinae. Entretanto, a fórmula cariotípica (18m+28sm+8st) parece ser específica para O. cf. polyodon, considerando as outras espécies de Hypoptopomatinae já analisadas.

Inversión inusual del cromosoma 21 en una paciente abortadora habitual / Chromosome 21 Inversioninusual in a Recurrent Abortion Patient

Las inversiones pericéntricas están entre los reordenamientos cromosómicos balanceados más usuales, con una frecuencia de un 1-2 %. Al laboratorio de citogenética del Centro Nacional de Genética Médica se remite una paciente con múltiples abortos del primer trimestre del embarazo. Se realizó el cariotipo en sangre periférica a una resolución de 450 bandas. La paciente presentó una inusual inversión pericéntrica del cromosoma 21 con la fórmula cromosómica 46,XX,inv (21) (p11.2 q21.1). Se discuten los posibles gametos resultantes de la segregación meiótica en esta paciente y se valoran los riesgos de abortos e hijos malformados teniendo en cuenta los puntos de ruptura en el 21.

Pericentric inversions are among the most frequent chromosomal rearrangements with a frequency of 1-2 %. A woman with repeated first trimester pregnancy loss was referred to cytogenetic laboratory of The National Center of Human Genetics. A karyotype conventional banding technique at resolution of ~450 was made. The patient presented an unusual pericentric inversion 46,XX,inv (21)(p11.2 q21.1). The possible gametes as result of crossover events (during the pachytene stage of meiosis I) were discussed. The risk of miscarriages and malformed children were evaluated according the breakpoint in 21 chromosome.

CARACTERIZACIÓN CITOGENÉTICA EN INDIVIDUOS DEL GÉNERO Lagothrix EN COLOMBIA (PRIMATES: ATELIDAE) / Cytogenetic Characterization in Individuals of the Genus Lagothrix in Colombia (Primates: Atelidae)

El género Lagothrix se encuentra representado en Colombia por Lagothrix lagothricha lagothricha y Lagothrix lagothricha lugens y siendo un género llamativo para el tráfico y caza, se han realizado varios trabajos encaminados a conocer sobre su ecología y ciclo de vida mostrando la importancia de este género en el ecosistema aunque sus características citogenéticas no han sido bien estudiadas. En este trabajo se analizaron 18 individuos (seis, L. l. lugens y 12 L. L. lagothricha) en cautiverio provenientes de zoológicos y centros de rescate, en los que por medio de técnicas de cultivo de sangre periférica y bandaje cromosómico G, C, R, Q y NOR se determinó un cariotipo estándar de 2n=62 para todos los individuos con dos variantes de éste también conocidos como cariomorfos que se originan por la diferencia en su número fundamental (NF), debido a una inversión pericéntrica en el par cromosómico 24. Dentro de estos cariomorfos se encontraron polimorfismos en varios pares cromosómicos que no fueron determinantes para diferenciar subespecies en los individuos trabajados, por lo que se recomienda revisar la taxonomía del género.

The genus Lagothrix is represented in Colombia by Lagothrix lagothricha lagothricha and Lagothrix lagothricha lugens but their cytogenetic features have not been well characterized. We studied 18 captive individuals (6, L. l. lugens and 12, L. L. lagothricha) from zoos and rescue centers, using techniques of peripheral blood culture and G, C, R, Q and NOR chromosome banding. We determined the standard karyotype 2n = 62 for all analyzed individuals with two karyotype variants (also known as karyomorphs) that showed different fundamental numbers due to a pericentric inversion on chromosome pair 24. Within these karyomorphs other polymorphisms were found in several pairs that were not crucial to distinguishing subspecies. We recommend reviewing the taxonomy of the genus especially at the subspecies level.

De Novo Pericentric Inversion of Chromosome 9 in Congenital Anomaly

PURPOSE: The pericentric inversion of chromosome 9 is one of the most common structural balanced chromosomal variations and has been found in both normal populations and patients with various abnormal phenotypes and diseases. The aim of this study was to re-evaluate the clinical impact of inv(9)(p11q13). MATERIALS AND METHODS: We studied the karyotypes of 431 neonates with congenital anomalies at the Pediatric Clinic in Ajou University Hospital between 2004 and 2008 and retrospectively reviewed their clinical data. RESULTS: Chromosomal aberrations were detected in 60 patients (13.9%). The most common type of structural abnormality was inv(9)(p11q13), found in eight patients. Clinical investigation revealed that all eight cases with inv(9)(p11q13) had various congenital anomalies including: polydactyly, club foot, microtia, deafness, asymmetric face, giant Meckel's diverticulum, duodenal diaphragm, small bowel malrotation, pulmonary stenosis, cardiomyopathy, arrhythmia, and intrauterine growth restriction. The cytogenetic analysis of parents showed that all of the cases were de novo heterozygous inv(9)(p11q13). CONCLUSION: Since our results indicate that the incidence of inv(9)(p11q13) in patients with congenital anomalies was not significantly different from the normal population, inv(9)(p11q13) does not appear to be pathogenic with regard to the congenital anomalies. Some other, to date unknown, causes of the anomalies remain to be identified.

Non-Synteny Regions in the Human Genome

Closely related species share large genomic segments called syntenic regions, where the genomic elements such as genes are arranged co-linearly among the species. While synteny is an important criteria in establishing orthologous regions between species, non-syntenic regions may display species-specific features. As the first step in cataloging human- or primate-specific genomic elements, we surveyed human genomic regions that are not syntenic with any other non-primate mammalian genomes sequenced so far. Based on the data compiled in Ensembl databases, we were able to identify 10 such regions located in eight different human chromosomes. Interestingly, most of these highly human- or primate-specific loci are concentrated in subtelomeric or pericentromeric regions. It has been reported that subtelomeric regions in human chromosomes are highly plastic and filled with recently shuffled genomic elements. Pericentromeric regions also show a great deal of segmental duplications. Such genomic rearrangements may have caused these large human- or primate-specific genome segments.

Incidence and Karyotypes According to Each Chromosome in 13 Cases with Inversion / 대한주산의학회잡지

PURPOSE: This study was aimed to evaluate the incidence and karyotypes according to chromosome in 13 cases with inversion detected by cytogenetic analysis. METHODS: The incidence of inversion was calculated and karyotypes of inversion were classified according to each chromosome in cases with inversion detected from 390 individuals who had undergone cytogenetic analysis in Hanyang University Hospital from January 2005 to February 2009. RESULTS: The overall incidence of inversions was 3.3% (13/390). All of 13 cases were heterozygotes for inversions. Among these 13 inversions, 12 cases (92.3%) were having pericentric inversions showing karyotypes of 46,XX,inv(9)(p11q13) in 7 cases, 46,XX,inv(9)(p11q12) in 2 cases, and one cases of 46,X, inv(Y)(p11.3q11.23), t(8;9)(q24.3;q34.1), 46,X, del(Y)(q12), inv(Y)(p10q11. 23) and 46,XY, inv(8)(p21q24.1) respectively. Last one case (7.7%) was having paracentric inversion showing a karyotype of 46,XX,inv(9)(q22.1q34.3). Classification according to each chromosome in 13 cases with inversion was that 10 of 13 cases (76.9%) were located in chromosome 9 (9 cases of pericentric inversions and a case of paracentric inversions), 2 of 13 cases (15.4%) in chromosome Y and 1 of 13 cases (7.7%) in chromosome 8. CONCLUSION: Although patients are phenotypically normal, they might be inversion carriers. In high risk patients, inversions are more frequent than normal population. Various types of inversion could be in different chromosomes. Classification of types of inversion are needed for further genetic counseling according to the types.

Chromosome polymorphism in Ancistrus cuiabae Knaack, 1999 (Siluriformes: Loricariidae: Ancistrini)

Cytogenetic and FISH analyses were performed in 30 Ancistrus cuiabae specimens from a bay near the town of Poconé, in the Pantanal of Mato Grosso, Brazil. The observed diploid number was 2n = 34 chromosomes for both sexes and three distinct katyotypic formulae were found, namely cytotype A (20m, 8sm, 6st, Fundamental Number/FN = 68; 6 males and 11 females), cytotype B (19m, 8sm, 6st, 1a, FN = 67; 8 males and 4 females) and cytotype C (18m, 8sm, 6st, 2a, FN = 66; a single male). NORs's analyses showed that these regions were located in distinct sites on the NOR-bearing chromosome pair, according to cytotypes. Thus, in cytotype A, NORs were located in the terminal region of the short arm of the second metacentric chromosome pair; in cytotype B, they were detected in the short arm of the metacentric chromosome and interstitially on the acrocentric chromosome and, in cytotype C, NORs were observed in the interstitial region of the acrocentric chromosome pair. C-positive heterochromatic bands were adjacent to the rDNA sites in the corresponding chromosomes. Thus, the chromosomal polymorphism of A. cuiabae was probably originated through a pericentric inversion in chromosome pair nº 2 involving the NOR sites, which represents a novelty in the Ancistrini tribe. The results also broaden the knowledge of the chromosomal evolution in Ancistrus, the most derived genus of the Ancistrini tribe.(AU)

Foram analisados, com técnicas convencionais de citogenética e FISH, 30 exemplares da espécie Ancistrus cuiabae da baía Arrombado, próximo a Poconé, Pantanal do Mato Grosso. Foram observadas metáfases com número diploide 2n = 34 cromossomos para ambos os sexos e três fórmulas cariotípicas distintas, aqui denominadas de citótipo A, verificado em 06 machos e 11 fêmeas (20m, 8sm, 6st, Número Fundamental, NF = 68); citótipo B, em 08 machos e 04 fêmeas (19m, 8sm, 6st, 1a, NF = 67) e citótipo C em apenas 01 macho (18m, 8sm, 6st, 2a, NF = 66). As NORs confirmaram os distintos citótipos verificados, além de evidenciar que os cromossomos portadores de rDNA são os que representam o polimorfismo na espécie Ancistrus cuiabae. No citótipo A, as NORs foram verificadas na região terminal do braço curto do segundo par de cromossomos metacêntricos; no citótipo B, foram evidenciadas no segundo par, heteromórfico, no braço curto do cromossomo metacêntrico e intersticial no seu homólogo acrocêntrico; no citótipo C as NORs foram observadas na região intersticial num par de cromossomos acrocêntricos. A análise da heterocromatina constitutiva evidenciou blocos discretos adjacentes ao rDNA no segundo par de cromossomos de ambos os citótipos. Uma provável inversão pericêntrica é a hipótese proposta para a origem deste polimorfismo na espécie Ancistrus cuiabae. Estes resultados ampliam o conhecimento sobre o gênero Ancistrus, o mais derivado da tribo, contribuem para o conhecimento sobre este grupo de peixes e para inferir sobre a evolução cromossômica dos Ancistrini(AU)

Pericentric Inversion of the X Chromosome in a Male with Azoospermia and in the Family of a Pregnant Female Carrier

We report on two cases of pericentric inversion of X chromosome. The cases were found in a 40-year- old man with azoospermia and in a family of a 38-year-old pregnant woman. The first case with 46,Y,inv(X)(p22.1q27) had concentrations of LH, prolactin, estradiol, and testosterone that were within normal ranges; however, FSH levels were elevated. Testis biopsy revealed maturation arrest at the primary and secondary spermatocytes without spermatozoa. There were no microdeletions in the 6 loci of chromosome Y. For the second case, the cytogenetic study of the pregnant woman referring for advanced maternal age and a family history of inversion X chromosome was 46,X,inv(X)(p22.11q27.2). The karyotype of her fetus was 46,X,inv(X)(p22.1q27). Among other family members, the karyotypes of an older sister in pregnancy and her fetus were 46,X,inv(X)(p22.11q27.2), and 46,Y,inv(X), respectively. The proband's father was 46,Y,inv(X)(p22.11q27.2). All carriers in the family discussed above were fertile and phenotypically normal. In addition, the ratio of inactivation of inv(X) by RBG-banding was discordant between the two sisters, with the older sister having only 4.1% of cells carrying inactivated inv(X) while the proband had a 69.5% incidence of late replicating inv(X). Therefore, we suggest that the cause of azoospermia in the first case might be related to inversion X chromosome with positional effect. Also, the family of the second case showing normal phenotype of the balanced inv(X) might be not affected any positional effect of genes.

Chromosome polymorphisms in natural populations of the South American grasshopper Sinipta dalmani

Six populations of Sinipta dalmani from the provinces of Buenos Aires and Entre Rios (Argentina) were analyzed. The populations of "El Palmar" National Park (Entre Rios) were polymorphic for pericentric inversions in pairs M4 and M7 and for a centric fusion involving pair M5 and the X chromosome. The M4 inversion remained similar over time and the karyomorphic frequencies did not depart from those expected according to the Hardy-Weinberg equilibrium. The analysis of chiasma frequency and distribution showed clear intra- and interchromosome effects of the different chromosome rearrangements. Both inversions and centric fusions were related with total or partial crossing over restriction in heterozygous condition, leading to a genetic differentiation between rearranged and non-rearranged chromosomes. The chromosome polymorphisms analyzed herein were associated with an increase in the number of terminal chiasmata both in the rearranged chromosomes (heterozygous centric fusion and homozygous M4 inversion) and in the other chromosomes (M4 inversion). Our results showed that the chromosome polymorphisms in S. dalmani may be associated with a significant decrease in genetic recombination, which may explain in part their maintenance in some areas of its geographical distribution.

Pericentric inversion of chromosome 9[inv(9)(p12q13)]: Its association with genetic diseases.

Background: The chromosomal polymorphism of short arms of acrocentric chromosomes and heterochromatin variation of Chromosomes 1, 9, 16 and Y have been reported in humans. The pericentric inversion of Chromosome 9 is commonly seen in normal humans and the frequency estimated to be 1 to 3% in general population and inherited in mendalian fashion or might occur spontaneously without any clinical significance. Aim: The aim of the study was to study the frequency of inv(9) and its clinical correlation with human genetic diseases. Materials and Methods:0 The chromosomal analysis using GTG-banding was carried out in 3,392 cases suspected with genetic diseases. Results: The pericentric inversion frequency of different chromosomes in our study was 1.24% and frequency of inv(9)(p12q13) was high (64.29%) compared to other pericentric inversions in our study. A high frequency (9.33%) of inv(9)(p12q13) was detected in children with dysmorphic features and congenital anomalies. Conclusion: As a high frequency of inv(9)(p12q13) detected in children with dysmorphic features, the inv(9) definitely have a role in the abnormal phenotype development. During inversion event there might be loss or suppression of euchromatin chromosome region and hence detailed chromosomal break point study is important to understand the clinical significance of the pericentric inversion of Chromosome 9.

A Case of Split Hand Split Foot Malformation Associated with Pericentric Inversion of Chromosome 9 / 대한주산의학회잡지

Split hand split foot malformation (SHFM) is a human developmental disorder characterized by a deep median cleft in the hands and feet, missing digits, and fusion of the remaining digits. The disease itself is considered to be very rare, affecting one out of 90,000 newborn babies. SHFM is genetically heterogeneous. To date, five SHFM loci have been mapped, to chromosome 2, 3, 7, 10 and X, respectively. We experienced a case of SHFM in a male neonate who had lobster-claw deformities of the hands and feet. The karyotype of his chromosome was 46,XY,inv (9) (p12q13). We report the case with the review of the associated literatures.

A Case of Trisomy 10p with Vertebral Anomaly and Hypospadias / 대한주산의학회잡지

Tisomy 10p syndrome is a rarely reported chromosomal abnormality with distinct craniofacial anomalies, severe growth and psychomotor retardation, osteoarticular anomalies, and organ malformations. Most of reported cases were due to translocation of 10p to the other chromosome. Rare causes are tandem duplication, maternal pericentric inversion, isochromosome formation. We experienced newborn infant with craniofacial anomaly, hypospadias and extra vertebra and rib. The characteristic craniofacial anomalies were frontal bossing, wide opened fontanel and suture line, sparse eyebrow, turtle beak mouth, Cytogenic analysis showed 46, XY, rec(10) dup(10p) inv (10)(p11.2q26.1). Karyotype of the father was normal(46, XY). However, karyotype of the mother showed 46, XX, inv(10)(p11.2q26.1). Therefore, chromosome 10 recombination resulting from a maternal pericentric inversion formed trisomy 10p. We report rare chromosome abnormality syndrome, trisomy 10p, with brief review.

A Case of Pericentric Inversion of Chromosome 5(p15.1q11.2 )

Pericentric inversion of chromosome 5 is a rare chromosomal aberration, which has familial inheritance in a few cases. Many reports demonstrated that the phenotype is similar to the criduchat syndrome. There are many problems regarding the clinical significance for genetic counseling and parental diagnosis. The authors encountered a male neonate who presented clinodactyly, campylodactyly, closed fists with 4th and 5th fingers overlapping the index and 3rd fingers, simian crease, the dorsiflexed 2nd toes, and poor sucking power, but without other characteristics of Edwards syndrome or cri-du-chat syndrome. Chrornosome studies from peripheral blood showed a 46, XY,inv(5)(p15.1q11.2) karyotype. We report the first case of pericentric inversion of chromosome 5 in Korea with a review of literature.

A Case of Pericentric Inversion of Chromosome 5(p15.1q11.2 )

Pericentric inversion of chromosome 5 is a rare chromosomal aberration, which has familial inheritance in a few cases. Many reports demonstrated that the phenotype is similar to the criduchat syndrome. There are many problems regarding the clinical significance for genetic counseling and parental diagnosis. The authors encountered a male neonate who presented clinodactyly, campylodactyly, closed fists with 4th and 5th fingers overlapping the index and 3rd fingers, simian crease, the dorsiflexed 2nd toes, and poor sucking power, but without other characteristics of Edwards syndrome or cri-du-chat syndrome. Chrornosome studies from peripheral blood showed a 46, XY,inv(5)(p15.1q11.2) karyotype. We report the first case of pericentric inversion of chromosome 5 in Korea with a review of literature.

Prenatal detection of de novo inversion of chromosome 9 with duplicated heterochromatic region and postnatal follow-up

We report the first de novo case of a heterochromatic duplication on the long arm of the chromosome 9, which then was pericentrically inverted at p11q13. This condition was detected prenatally and carry to term. We then performed the follow up for over 1 year. So far, there seems to be no phenotypical abnormalities.

Familial Chromosome No. 9 Pericentic Inversion Producing Scimitar Syndrome

Scimitar syndrome is a rare congenital anomaly that is characterized by hypoplasia of the right lung and the right pulmonary artery with anomalous pulmonary venous drainage to the inferior vena cava. The scimitar vein is usually visible on chest radiographs, but may be obscured by the heart. It is essential for surgical correction to establish the point of drainage of the anomalous vein and associated anomalies. There are recent reports of familial total anomalous pulmonary venous return suggesting heritable forms of this anomaly. Although genetic factors are believed to have important roles in congenital heart disease, few genes involved in heart development have been located. We report a case of familial chromosome 9 inversion with Scimitar syndrome in an offspring who presented with dextrocardia. Evaluation with magnetic resonance cineangiograph imaging demonstrated an anomalous pulmonary vein draining into the inferior vena cava above the diaphragm and hypoplasia of the right lung and the right pulmonary artery. Chromsome analysis showed pericentric inversion of chromosome 9, inv 9 (p13, q21), in the patient and his mother as well. A brief review of the related literature is also included.

A Case of Bilateral Split Hand and Foot Malformation with Inversion of Chromosome 7

Split hand and split foot(SHSF) is a human developmental defect characterized by missing digits, fusion of remaining digits, and a deep median cleft resulting in a clawlike appearance of the hands and feets. SHSF is usually inherited in an autosomer dominant fashion. The incidence of SHSF is between 1/10,000 and 1/90,000. Thirteen cases of SHSF and chromosomal aberrations involving 7q21-22 have been described so far in the world. We experienced a case of typical tetramelic SHSF in neonate. Chromosome studies showed a pericentric inversion of chromosome 7:46,XY,inv(7) (p22q22). Inspection of the extremities and chromosome studies in the parents were normal.