Análisis clínic y molecular de una pacientecon pentasomia del cromoooma x. / Clinical and Molecular Analysis of a Patient with X-Chromosome Pentasomy.

Introducción: la Pentasomia del X (49,XXXXX) es una alteración cromosómica poco frecuente, que afecta a mujeres y fue descrita en 1963 por Kesaree y Wooley. Hasta la fecha se han reportado menos de 30 casos en la literatura. Se presenta un caso de pentasomia del cromosoma X, y mediante técnicas de biología molecular (microsatélites) se determino el origen materno de los cromosomas X adicionales. Caso clínico: paciente de 28 meses, con talla baja proporcionada, braquicefalia, fascies característica, genitales externos femeninos con labios mayores hipoplásicos, braquidactilia, clinodactilia bilateral del quinto dedo, luxación de rodilla derecha, deformidad en varo. Se realizó cariotipo en sangre periférica que reportó un complemento cromosómico 49,XXXXX. Materiales y métodos: se realizó extracción de ADN y PCR para la amplificación de ocho microsatélites o STR’s tetra y dinucleotídicos situados a lo largo del cromosoma X. Los productos amplificados se analizaron en el secuenciador ALF EXPRESS. Con la información alélica se realizó la construcción del haplotipo y el análisis de dosis génica mediante la determinación del área bajo la curva. Resultados y discusión: el análisis de los ocho STR’s realizados en la paciente y sus padres, permitió establecer que los cromosomas X extras corresponden a información alélica heredada de la madre. Se analizan los resultados y los eventos que se han documentado como relacionados con los fenómenos de no disyunción. Conclusión: el origen de la doble no disyunción que generó la pentasomia es materna, en donde un ovulo tetrasómico, con cuatro copias de cromosoma X fue fecundado con un espermatozoide monosómico normal.

Introduction: Pentasomy X is a rare chromosomal disorder which affects women. It was first described in 1963 by Kesaree and Wooley. Up to date, less than 30 cases have been reported. We report a case of 28 month old female patient with clinical features of Pentasomy X. Cytogenetic and molecular analysis revealed that her karyotype was 49,XXXXX and that the additional X chromosomes were maternal in origin. Case report: We present a 28 month old female patient with short stature, brachycephaly, characteristic facies, with female external genitalia, hypoplasic labia majora, brachydactyly, bilateral clinodactyly of the fifth finger, dislocation of the right knee with genu varum deformities. Chromosome analysis revealed a karyotype of 49, XXXXX. Materials and methods: We performed DNA extraction and subsequent PCR amplification of 8 microsatellites (STR’s) throughout the X chromosome. The amplified products were analyzed in the ALF EXPRESS sequencer. The allelic information obtained was used to construct haplotypes and to analyze gene dosage through the determination of the area under the curve. Results and discussion: Through the analysis of eight STR’s in the patient and her parents we were able to determine that the extra X chromosomes were inherited from the mother. We analyze our results and other well documented events that have been related to non-disjunctions. Conclusion: We confirmed through molecular analysis of X-linked DNA markers that the aneuploidy developed from two maternal non-disjunctions.

A Cytogenetic Study in Patients with Sex Chromosome Abnormalities / 소아과

PURPOSE: This study was performed to evaluate the recent frequency of karyotypes in different sex chromosome abnormalities and to evaluate the age and clinical manifestations at diagnosis. METHODS: Peripheral blood leukocytes were obtained from subjects who were clinically suspected to have sex chromosome abnormalities and referred to the cytogenetic laboratory in the Department of Pediatrics, Kyungpook National University Hospital from February 1981 to August 2001. RESULTS: The relative frequencies of different sex chromosome abnormalities were Klinefelter (52 percent), Turner (42 percent), XXX syndrome (3 percent) and mixed gonadal dysgenesis (3 percent). The populations of different karyotypes in Klinefelter syndrome were 47, XXY (97 percent) and 46, XY/ 47, XYY (3 percent). The populations of different karyotypes in Turner syndrome were 45, X (67 percent, ), mosaicism (23 percent), and structural aberrations (10 percent). The populations of different karyotypes in XXX syndrome were 47, XXX (67 percent, ) and 46, XX/47, XXX (33 percent). All mixed gonadal dysgenesis were 45, X/46, XY. Eighty one percent of sex chromosome abnormalities was diagnosed after puberty. Patients diagnosed with Klinefelter and Turner syndrome in infancy showed nearly normal phenotypes or had minor congenital malformations. CONCLUSION: Early diagnoses of sex chromosome abnormalities is required to prevent associated morbidities and to maximize growth and development. We have to pay careful attention in diagnoses of Turner syndrome because of the high proportion of mosaicism and structural aberrations.

Prenatal diagnosis and clinical analysis of fetal sex chromosome abnormalities / 重庆医科大学学报

Objectives:To analyze the association between fetal sexchromosome abnormalities and various high-risk indications during pregnancy. Methods:mid-trimester amniocentesis was used to detect fetal sex chromosomes in 2 346 high-risk pregnant women. Results:Among the 16 cases of abnormal sex chromosome,there were 3 cases of 45,X,1 case of 45,X/46,XX ,1 case of 45,X/46,X,i (X)(q10;q10),1 case of 45,X/46,XX,del(X)(q11),1 case of 46,X,i(X)(q10;q10),4 cases of 47,XXY,1 case of 47,XYY,2 cases of 47,XXX,1 case of 46,XY/47,XXY,and 1 case of 46,XX,inv9(X). Conclusion:To reduce the number of abnormal fetuses, invasive prenatal diagnostic techniques are feasible tools for confirming fetal sex chromosomes abnormalities. Advanced maternal age, positive serum screening results or ultrasound shows fetal abnormalities or fetal hygroma were associated with a higher frequency of fetal sex chromosome abnormalities.

A Clinical Study of Sex Chromosomal Abnormalities / 대한산부인과학회잡지

To provide current information on sex chromosome abnormalities to obstetricians andgynecologists who encounter such diagnoses and who counsel prospective parents faced withthe prenatal diagnosis of a sex chromosome abnormalities. I reviewed 116 patients' clinical data and results of karyotype which proven sexchromosome abnormalities in cytogenetic unit of Department of Ob. and Gyn., PNUH during theperiod of 1993. Aug.~1996. Dec.The results of the analysis of karyotyping in sex chromosome abnormalities in these 116cases are like following.1. Peak age group when diagnosed abnormal sex chromosome is 26~35 years old inmen(46 among 56 cases) and 16~30 years old in women(40 among 60 cases).2. The most common primary reason of abnormal sex chromosome is sterility inmen(48 among 56 cases) and amenorrhea in women(36 among 60 cases).3. The most common referred primary reason in Klinefelters syndrome issterility(44 among 49 cases) and in Turners syndrome is primary amenorrhea(27 among55 cases).4. The most common type of abnormal sex chromosome is Klinefelters syndrome inmen(49 among 56 cases) and Turners syndrome in women(55 among 60 cases).5. In my 116 cases of abnormal sex chromosome, numerical abnormalities are 67 cases,mosaicisms 28 cases, structural abnormalities 13 cases, XY female 6 cases, and XX male2 cases. So the most common abnormal sex chromosome is numerical abnormality.6. In my 55 cases of Turners syndrome, XO karyotypes are 26 cases, X, abnormal X are11 cases, and mosaic pattern are 18 cases. So the most common karyotype in Turnerssyndrome is standard pattern(45,X).In conclusion, abnormal sex chromosome were very important causes of infertility,amenorrhea, abnormal pubertal development, ambiguous genitalia, and stature. Therefore,these patients must taken cytogenetic study, and obstetrics and gynecologists provideaccurate and comprehensive genetic counseling.