45,X/46,X,psu dic(Y) gonadal dysgenesis: influence of the two cell lines on the clinical phenotype, including gonadal histology.

A child born with ambiguous genitalia (Prader III) was found to have a 45,X[92.2%]/46,X,psu dic(Y)(p12)[7.8%] karyotype in peripheral blood lymphocytes. The testosterone level was consistent with that of a normal male; however, gonadotropins were elevated. Ultrasound and endoscopy of the urogenital sinus revealed well-developed Müllerian structures. At 3.5 months, the child was operated for right-sided incarcerated hernia, and the gonad situated at the inguinal region was biopsied and classified as primitive testis. Based on the presence of Müllerian structures, anatomy of external genitalia and wish of the parents, the child was assigned female gender. She underwent removal of the left gonad at 4 months during another acute surgery; histology was similar to the right gonad. The rest of the right gonad was removed at 16 months, and feminizing genitoplasty took place at 3 years. The right and left gonad contained 28 and 22% of cells with a Y chromosome, respectively. During further histological examination, dysgenetic features of the gonads were discovered. Some germ cells displayed abnormal development based on the specific expression of immunohistochemical markers (OCT3/4, TSPY, KITLG), indicating a possible risk for future malignant germ cell tumor development. Contribution of the 45,X cell line to the phenotype was also observed: the patient developed celiac disease, and her growth pattern resembled that of Turner syndrome responding to growth hormone treatment.

[Case reports of patients with a marker chromosome]. / Kazuistiky pacientu s marker chromozómy.

Small, usually supernumerary chromosomes, denoted as marker chromosomes or markers, can be represented by various phenotypic expression, that depends on their origin and extent. Our article presents results of molecular cytogenetic analysis (FISH) of 34 patients with identified marker chromosome. In 21 cases a marker derived from acrocentric chromosome was identified, in 9 cases markers of gonosomal origin [der(X), der(Y)], and in 4 patients markers of some other chromosomes (5, 17, 18) were proved. The most frequent marker was that originating from chromosome 15 (8 cases). Two patients with different phenotype, markedly influenced by the extent of pseudoizodicentric chromosome 15 are described. In accordance with hitherto presented data, presence of supernumerary copies of the critical region PWACR (it is the partial trisomy, resp. tetrasomy 15q11-q13) in majority of cases brings about serious affection described as syndrome of the inverted duplication of chromosome 15. The most typical symptoms are psychomotoric retardation, hypotony, neurological symptoms and autistic features. The article stresses the importance of FISH method in the prenatal examination of marker chromosomes.

[Chromosome analysis in medicine]. / Chromozomální vysetrení v medicíne.

Aberrations of the normal number and structure of chromosomes can cause mental, growth and developmental delay, defects of sexual development, congenital defects, abnormal facial features, deformation of extremities, defective intrauterine development, spontaneous miscarriages, and infertility. Expressive changes of the karyotype are used to be found in cancer cells. In majority of cases a lot of genes are abundant or deleted and then many organs are affected--therefore disorders are described as "syndromes". Down and Turner syndromes are the best known syndromes caused by numerical aberrations of human chromosomes. In the diagnostics of structural aberrations, the use of methods of classical cytogenetics becomes limited. Fluorescence in situ hybridisation (FISH) is therefore used more frequently. FISH method has several advantages: rapidity, sensitivity, specificity and possibility to apply this method also in interphase nuclei. Application of FISH allows us to detect submicroscopic deletions and amplifications and to explain the aetiology of inborn developmental defects and cancer diseases (including familiar cases). The newest FISH modifications perform one step analysis of multiple chromosomal rearrangements and help us to ascertain the diagnosis and the prognosis of cancer diseases. The use of special computer software for chromosomal and FISH analysis is the most important part of the current cytogenetic diagnostics.