XY Karyotype (xy + karyotype)

Distribution by Scientific Domains

Selected Abstracts

Heterozygous SOX9 Mutations Allowing for Residual DNA-binding and Transcriptional Activation Lead to the Acampomelic Variant of Campomelic Dysplasia,

HUMAN MUTATION, Issue 6 2010
Alex Staffler
Abstract Campomelic dysplasia is a malformation syndrome with multiple symptoms including characteristic shortness and bowing of the long bones (campomelia). CD, often lethal due to airway malformations, is caused by heterozygous mutations in SOX9, an SRY-related gene regulating testis and chondrocyte development including expression of many cartilage genes such as type II collagen. Male to female sex reversal occurs in the majority of affected individuals with an XY karyotype. A mild form without campomelia exists, in which sex-reversal may be also absent. We report here two novel SOX9 missense mutations in a male (c.495C>G; p.His165Gln) and a female (c.337A>G; p.Met113Val) within the DNA-binding domain leading to non-lethal acampomelic CD. Functional analyses of mutant proteins demonstrate residual DNA-binding and transactivation of SOX9-regulated genes. Combining our data and reports from the literature we postulate a genotype-phenotype correlation: SOX9 mutations allowing for residual function lead to a mild form of CD in which campomelia and sex reversal may be absent. © 2010 Wiley-Liss, Inc. [source]

Prenatal diagnosis and postnatal follow-up of a child with mosaic trisomy 22 with several levels of mosaicism in different tissues

Vincenzo Mazza
Abstract We report on the case of a patient with mosaic trisomy 22, who was diagnosed prenatally by amniocentesis during the 16th week of pregnancy. In the foetus, three trisomic clones were found out of the nine that were analyzed (the other six clones had a 46,XY karyotype). Cytogenetic analysis of cord blood during the 20th week of pregnancy showed a normal male karyotype; however, a placental biopsy that was performed at the same time showed 100% and 95% trisomic cells in the chromosomal analysis of direct and long-term cultures, respectively. A follow-up ultrasonographic examination excluded major congenital malformations and the abdominal and cranial circumferences were normal until the 24th week of pregnancy. At this point, a deflection of the growth curve occurred and the values were persistently below the 3rd centile until birth. After birth, karyotypic and fluorescent in situ hybridisation analyses performed on the fibroblasts of the neonate showed that 3,4% of the cell lines were trisomic, and studies using microsatellite markers showed normal allelic segregation, which excluded uniparental disomy. The period of postnatal follow-up was characterised by a significant growth deficit (height and head circumference were less than the 3rd centile) and by mental retardation. The present case is compatible with other earlier reports that showed that the levels of trisomy 22 are tissue-specific and are of little help in establishing the prognosis of the chromosomal abnormality. [source]

Graham Little,Piccardi,Lassueur syndrome associated with androgen insensitivity syndrome (testicular feminization)

J Vega Gutiérrez
ABSTRACT Graham Little,Piccardi,Lassueur syndrome is characterized by the presence of cicatricial alopecia on the scalp, keratosis pilaris in the skin of trunk and extremities, and non-cicatricial hair loss in pubis and axillae. A frequent form of male pseudohermaphroditism is complete androgen insensitivity syndrome (CAIS), also known as testicular feminization syndrome. It refers to genetic males with XY karyotype who, owing to a lack of sensitivity in the peripheral androgenic receptors, develop a female phenotype. Axillary and pubic hair is typically scarce or absent. To our knowledge, this is the first case describing the association of the two processes. The presence of both processes in the same patient furthers our understanding of Graham Little,Piccardi,Lassueur syndrome as it rejects the influence of androgens in the alopecias accompanying this syndrome. The coincidence of non-cicatricial alopecia in axillary and pubic hair in both processes is also remarkable. [source]

Application of QF-PCR for the prenatal assessment of discordant monozygotic twins for fetal sex

F. J. Fernández-Martínez
Abstract Objective To establish the utility of quantitative fluorescent polymerase chain reaction (QF-PCR) in order to determine the zygosity of multiple pregnancies, as well as to define the origin of the most frequent aneuploidies in amniotic fluid samples. Methods We describe the case of a monochorionic (MC) diamniotic (DA) pregnancy with phenotypically discordant twins (nuchal cystic hygroma and non-immune hydrops in twin A and no anomalies in twin B). QF-PCR was performed for rapid prenatal diagnosis in uncultured amniocytes and subsequently in cultured cells. Polymorphic markers for chromosomes X, Y, 13, 18 and 21 were used for determination of zygosity as well as sex chromosome aneuploidy. Results Twin A showed a Turner Syndrome (TS) mosaicism pattern by QF-PCR in uncultured amniocytes. The monozygotic origin of the pregnancy was determined. Interphase fluorescence in situ hybridization (I-FISH) in this sample showed a mosaicism X0/XY (83/17%). Cytogenetic analysis revealed a 45,X0 karyotype in twin A and a 46,XY karyotype in twin B. Conclusions QF-PCR is a reliable tool for the determination of the zygosity independently of the chorionicity and the fetal sex in case of twin pregnancy. Testing both direct and cultured cells can provide useful results for genetic counselling in chromosomal mosaicisms. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Complex de novo cryptic subtelomeric rearrangements in a fetus with multiple ultrasonographic abnormalities and a normal karyotype at amniocentesis

M. Anwar Iqbal
Abstract Objective Prenatal diagnosis is usually offered to the majority of pregnancies with fetal structural abnormalities detected by prenatal ultrasound; however, only a small proportion show an abnormal karyotype. We wanted to detect cryptic subtelomeric rearrangements (CSTR) in a fetus with multiple abnormal ultrasonographic findings that revealed a normal karyotype at amniocentesis. Methods Fetal chromosome analysis was performed from amniotic fluid cells. Parental chromosome analysis was done on PHA stimulated lymphocyte cultures. For fluorescence in situ hybridization (FISH) analysis, ToTelVysion multicolor DNA probe mixture was used to hybridize the p and q telomeres of each chromosome. Results The amniotic fluid chromosome analysis revealed an apparently normal 46,XY karyotype. A follow-up FISH analysis showed three apparently balanced complex translocations involving (1) the chromosome 4p and 22q telomeres (2) 4q and 11q telomeres and (3) 8p, 20p and 20q telomeres. Parental chromosome and subtelomere FISH analysis was found to be normal. Conclusion To our knowledge, this is the first report of complex de novo cryptic translocations in an abnormal fetus. These CSTR identified by FISH with subtelomere-specific probes are not detected by other cytogenetic and/or molecular cytogenetic approaches. However, to confirm the balanced nature of CSTR, array-CGH can be helpful. Further studies are in progress to determine the frequency of CSTR and its significance in the etiology of fetal abnormalities. Copyright © 2005 John Wiley & Sons, Ltd. [source]

A further case of confined placental mosaicism for trisomy 2 associated with adverse pregnancy outcome

Eileen Roberts
Abstract Objectives To add to the knowledge base concerning confined placental mosaicism for trisomy 2. Methods Cytogenetic study of a late CVS referred for hyperechogenic bowel and raised AFP, and cytogenetic and molecular genetic study of a follow-up amniocentesis. Ultrasound monitoring at regular intervals following the CVS result. Results All cells examined from direct and cultured CVS showed a 47,XY,+2 karyotype. Amniocentesis showed a mosaic 47,XY,+2[8]/46,XY[81] karyotype. Uniparental disomy (UPD) studies on the amniotic fluid showed normal biparental inheritance. The pregnancy developed oligohydramnios and IUGR and resulted in a 26-week liveborn male infant with a 46,XY karyotype, which died after 3 days because of complications of severe prematurity. Placental villi post delivery showed only the 47,XY,+2 cell line. Conclusions This case represents a further example of confined placental mosaicism (CPM) for trisomy 2 associated with oligohydramnios, IUGR and poor pregnancy outcome. Copyright © 2003 John Wiley & Sons, Ltd. [source]

A 19 Year Old with Complete Androgen Insensitivity Syndrome and Juvenile Fibroadenoma of the Breast

Steven E. Davis MD
We report a case of a 19-year-old female with complete androgen insensitivity syndrome (CAIS) who was diagnosed with a juvenile fibdroadenoma of the breast. The patient presented at age 18 with primary amenorrhea. She had been raised as a female and went through thelarche at age 13 and adrenarche at age 14. She had two sisters and three maternal aunts with androgen insensitivity syndrome. Physical exam revealed that the patient had no cervix, and a pelvic sonogram confirmed that the uterus was absent. Genetic analysis revealed a 46 XY karyotype. Bilateral intra-abdominal testes were noted on ultrasound and subsequently removed. She was placed on synthetic estrogen replacement therapy. Roughly 1 year following orchiectomy, the patient noticed an enlarging mass in her right breast. Physical exam revealed a roughly 5 cm mobile mass in the upper portion of the nipple-areolar complex. Ultrasound showed a solid mass consistent with a fibroadenoma. Because of the size of the lesion and the patient's hormonal make-up, a fine needle aspirate was obtained. Cytopathology showed large cohesive sheets of ductal epithelial cells, scattered histiocytes, numerous bare nuclei, fragments of fibrous tissue and metachromatic stroma. Some of the stroma was noted to be cellular. The tumor was subsequently excised. Microscopically, the lesion had epithelial and stromal hyperplasia consistent with a fibroadenoma. Phyllodes-like qualities of large size, increased stromal cellularity, and intracanalicular growth ("leaf-like projections") were noted; however, the pathologist found that the florid epithelial hyperplasia and the patient's young age were more compatible with a juvenile fibroadenoma. We describe what we believe to be the first report of a patient with CAIS and a fibroadenoma of the breast. The hormonal imbalance typically found in these patients, combined with the fact that most individuals with CAIS receive exogenous estrogen therapy, suggests that there may be a relatively high incidence of fibroadenoma in these patients. [source]