INTRODUCTION: The traditional cytogenetic analysis requires relatively long cell culture time, intensive labour and trained personnel. But, in clinical situations, rapid diagnosis of genetic disease is very important for urgent decision for future management. So we need more rapid and precise diagnostic tools for clinical genetic counselling. The fluorescence in situ hybridization (FISH) has been studied for detecting chromosomal aneuploidies because this method can get rapid and precise results of cytogenetic studies. OBJECTIVE: To evaluate the clinical utility of fluorescence in situ hybridization technique as a diagnostic tool of chromosomal anomaly. METHODS: Peripheral blood or gonadal tissue were obtained from the patients (n=63) clinically suspicious of genetic disease. Chorionic villi (n=6), amniotic fluid (n=9), and fetal cord blood (n=2) were obtained from 15 pregnancies undergoing fetal karyotyping at 9 to 30 weeks of gestation for prenatal genetic counselling. Karyotyping was performed by both traditional cytogenetics and FISH, using commercially available kits. After the procedures, the results of FISH were compared with the results of traditional cytogenetic studies. RESULTS: In a blind series of 17 samples all, including trisomy 21 (1 case), trisomy 18 (1 case), monosomyX (1 case), 47,XYY (1 case), and 47,XXY (1 case), were correctly identified. FISH results were correspondent with conventional karyotyping results in 7 patients with intersex except one case of suspicious of mosaicism. In nine children of Turner syndrome, the results of two methods were correspondent too. There was a fluorescent signal defect in band 15 q11-q13 in one of chromosome 15 in 18 children of 29 patients, clinically suspicious of Prader-Willi syndrome, with FISH method and only four patients were diagnosed as Prader-Willi syndrome with G-banding microscope. It was impossible to identify the defect in chromosome 15 q11-q13 in 10 (34%) children by both methods. Two children of 11 patients, clinically suspicious of Angelman syndrome, were diagnosed as Angelman syndrome with both method respectively. And four children were diagnosed as Angelman syndrome only with FISH method. In 5 cases, we cannot detect the defect in chromosome 15 q11-q13 with both methods. In four cases of Williams syndrome, the results of both methods were as follows; 1 case (25%): diagnosed as Williams syndrome by both methods; 2 cases (50%): diagnosed
Amniotic Fluid ; Aneuploidy ; Angelman Syndrome ; Cell Culture Techniques ; Child ; Chorionic Villi ; Chromosomes, Human, Pair 15 ; Cytogenetic Analysis ; Cytogenetics ; Diagnosis* ; Down Syndrome ; Female ; Fetal Blood ; Fluorescence* ; Gonads ; Humans ; In Situ Hybridization* ; Karyotyping ; Mosaicism ; Prader-Willi Syndrome ; Pregnancy ; Trisomy ; Turner Syndrome ; Williams Syndrome

A chromosomal study was performed in a tota1 of 98 patients with suspected Y chromosomal abnormalities during past 1-1/2 years (Feb. 1984 -Aug. 1985). Karyotypes were obtained using short-term blood culture. Of these 43 (44%) patients had abnormal chromosome complements. Among all patients with chromosome abnormalities, 88% (38/43) had aberrations of chromosome number and others 32% (5/42) had aberrations of chromosome structure. The results of chromosomal study in various groups showed as follows: l. In 34 cases of Klinefelter's syndrome, there were 31 cases (91%) of 47,XXY, 1 case of 46,XX,47, XXY, 1 case of 48, XXXXY and 1 case of 46,XX/46,XY/47,XXY. 2. AII 3 cases of mixed gonadal dysgenesis had 45,X/46,XY. 3. l case of true hermaphroditism had 46,XX. 4. Z cases of male Turner`s syndrome, 6 cases of male pseudohermaphroditism and 1 case of agonadism had 46,XY. 5. In 6 cases of female pseudohermaphroditism, there were 4 cases of 46,XX, 1 case of 46,XX, inv(9) and 1 case of 46,XX, t (14q, 21q). 6. In 28 cases of hypogonadism (excluding Klinefelter`s syndrome), there were 25 cases (89%) of 46, XY, 1 case of 46,XY, 15s-, 1 case of 46,XY, inv(9) and 1 case of 46,XY/46, XY,t(7 : 14). 7. 1 case of cryptorchism had 47,XY,+21. 8. All of 5 cases of hypospadia, 5 cases of cryptorchism, 3 cases of hypospadia with cryptorchism, 2 cases of small phallus, 1 case of concealed penis and 1 case of normal male who wanted to correct his registered sex had 46,XY.
46, XX Disorders of Sex Development ; 46, XY Disorders of Sex Development ; Chromosome Aberrations* ; Chromosome Structures ; Complement System Proteins ; Cryptorchidism ; Cytogenetics* ; Down Syndrome ; Female ; Gonadal Dysgenesis, Mixed ; Humans ; Hypogonadism ; Hypospadias ; Karyotype ; Klinefelter Syndrome ; Male ; Ovotesticular Disorders of Sex Development ; Penis ; Y Chromosome

PURPOSE: The objectives were to examine following 2 questions related to cognitive profile for the children with Williams syndrome (WS); 1) Is there a significant advantage for verbal IQ over performance IQ in WS?; 2) Is there selective impairment in visuospatial ability in the children with WS? MATERIALS AND METHODS: Five children with WS with the age of 90.86+/-20.73 months were compared with 12 children with Prader-Willi syndrome (PWS) or Down syndrome (DS) with comparable age and IQ. RESULTS: All 5 children with WS showed intellectual disability whose mean scaled scores were 15.71+/-9.27 in verbal subtests and 14.29+/-7.50 in performance subtests, which did not show significant difference. There was no significant difference in the total sum of scaled scores of verbal subtests among WS, PWS and DS. There was no selective impairment in subtests which represented visuospatial tasks for the children with WS. However, the scaled score of object assembly was significantly lower in WS (2.29+/-0.95) compared to that of PWS (4.75+/-2.77; P<0.05). CONCLUSION: The general notion that the children with WS would be relatively strong in verbal function when compared with their overall cognitive function was not observed in this study. The verbal function of the children with WS was not better when compared to the children with DS or PWS. There was no selective impairment of visuospatial function in the children with WS at this age. However, the visuospatial function was significantly low in the children with WS only when compared to the children with PWS.
Child ; Down Syndrome ; Humans ; Imidazoles ; Intellectual Disability ; Nitro Compounds ; Prader-Willi Syndrome ; Williams Syndrome

PURPOSE: We have performed this study to obtain reference data for the distribution of chromosomal aberrations in Korea. METHODS: We analyzed 1,180 chromosomal study cases from Kwang ju Christian Hospital during the past 25 years. 756 cases suspected of characteristic chromosomal aberration syndromes and 424 cases with hermaphroditism, mild sexual abnormalities, multiple anomalies, or mental and growth retardation were included. RESULTS: The male to female ratio of autosomal aberration syndromes was 1.2 : 1. 78.6% of autosomal aberrations were diagnosed under 1 year of age, whereas 89.8% of sex chromosomal aberrations were diagnosed over 12 years of age. Among 1,180 cases, 612 ones had chromosomal aberrations(51.9%) : 590 of 756 cases suspected of chromosomal aberration syndromes had aberrations(78.0%), whereas 22 of 424 showing the above other features had aberrations(5.2%). Autosomal aberrations appeared in 514 cases(83.8%) and sex chromosomal aberrations appeared in 98 cases(16.2%). The most frequently observed abberation in autosomal aberrations was Down syndrome, followed by E, D, B, A and C group aberrations. The most common abberation in sex chromosomal aberrations was Turner syndrome, followed by Klinefelter syndrome and Fragile X syndrome. CONCLUSION: It is of vital importance that patients suspected of chromosomal aberrations undergo chromosomal analysis. Further advanced chromosomal staining and molecular genetic methods will raise the detection rate of chromosomal aberrations.
Abnormalities, Multiple ; Chromosome Aberrations* ; Disorders of Sex Development ; Down Syndrome ; Female ; Fragile X Syndrome ; Gwangju ; Humans ; Klinefelter Syndrome ; Korea ; Male ; Molecular Biology ; Turner Syndrome

Turner syndrome is the most common chromosomal disorder in girls. Various phenotypic features show depending upon karyotype from normal female through ambiguous genitalia to male. Usually, Turner girls containing 45,X/46,XY mosaicism, or sex-determining region Y (SRY) gene may have mixed gonadal dysgenesis with various external sexual differentiation. We experienced a short statured 45,X Turner girl with normal external genitalia. Because SRY gene was positive, laparoscopic gonadectomy was performed. The dysgenetic gonads revealed bilateral ovotesticular tissues. The authors report a mixed gonadal dysgenesis case found in clinical 45,X Turner patient with positive SRY gene. Screening for SRY gene should be done even the karyotype is 45,X monosomy and external genitalia is normal.
Chromosome Disorders ; Disorders of Sex Development ; Female ; Genes, sry* ; Genitalia ; Gonadal Dysgenesis, Mixed* ; Gonads ; Humans ; Karyotype ; Male ; Mass Screening ; Monosomy ; Mosaicism ; Sex Differentiation ; Turner Syndrome*

45,X/46,XY mosaicism is a rare disorder with a wide heterogeneity in its manifestations. An 18-year-old girl was referred to the endocrine clinic for investigation of her primary amenorrhea. Clinical examination was unremarkable. Hormonal profile was consistent with primary ovarian insufficiency and human chorionic gonadotropin (hCG) stimulation did not show evidence of active testicular tissue. Karyotyping studies by G-banding revealed a 45,X/46,XY karyotype. She was diagnosed with mosaic Turner syndrome with Y chromosomal material and investigation was performed to identify the presence of male gonads due to the risk of gonadal malignancy. Magnetic resonance imaging (MRI) of the pelvis did not show evidence of gonads. Laparoscopic exploration was proposed but the patient and parents refused opting for conservative management. This case highlights the challenges in the management of this rare condition.
Gonadal Dysgenesis, Mixed ; Turner Syndrome ; Y Chromosome

Disorders of sexual development (DSD) defined as congenital conditions associated with atypical development of anatomical, gonadal or chromosomal sex, is a rare condition that may present with ambiguous genitalia. Included in the varied classes of DSD is mixed gonadal dysgenesis which is known to be due to mosaicism, a chromosomal aberration. Mosaic individuals may have concerns on growth, hormone balance, gonadal development, sex of rearing and fertility. This case report presents an 18-year old student who presented with primary amenorrhea, delayed secondary sexual characteristics and phenotypic features of Turner syndrome who, on chromosomal analysis revealed 45X0/46XY mosaicism. The patient underwent operative laparoscopy with bilateral gonadectomy on the basis of the increased risk of development of gonadal malignancy in phenotypic females with Y-chromosome material. Histopathological analysis revealed bilateral streak gonads. Hormone replacement therapy was then initiated for the induction of secondary female sex characteristics, as treatment for estrogen deficiency, for the induction of pubertal growth spurt and for optimization of bone mineral accumulation. Management of disorders of sexual development is challenging, thus the need for a multidisciplinary approach involving experts in endocrinology, gynecology, psychology and genetics.
GONADAL DYSGENESIS, MIXED ; MOSAICISM ; TURNER SYNDROME ; CASTRATION

Mental retardation is a disability characterized by significant limitations both in intellectual functioning and in adaptive behavior as expressed in conceptual, social, and adaptive skills, which originates before the age of 18. The prevalence of mental retardation among elementary school children in Korea is estimated as 9~12/1,000. In most cases of mental retardation, the interplay of genetic and environmental influences remains poorly understood. However, recent advances in molecular genetic techniques have enabled us to understand more about the molecular basis of several genetic syndromes associated with mental retardation. This article presents a review of three common genetic conditions causing mental retardation-Down syndrome, fragile X syndrome, and Prader-Willi syndrome-with the summary of the effectiveness of early intervention for the children with mental retardation.
Adaptation, Psychological ; Child ; Down Syndrome ; Early Intervention (Education) ; Fragile X Syndrome ; Humans ; Intellectual Disability* ; Korea ; Molecular Biology ; Prader-Willi Syndrome ; Prevalence

PURPOSE: We investigated the clinical characteristics and relationship between chromosome and its phenotypic expression in patients with 45 XO/46XY mosaicism or 45 XO with SRY gene. MATERIALS AND METHODS: 11 patients with 45XO/46XY chromosomal abnormality and 4 patients with 45XO with SRY positive reaction admitted from 1990 to 1996 were evaluated. Patients were grouped according to chromosome and gonadal expression. Group A consisted of patients with 45XO/46XY chromosome and unilateral streak gonad, group B patients with 45XO chromosome, SRY positive reaction and unilateral streak gonad and group C patients with 45XO/46XY chromosome and bilateral streak gonads. RESULTS: Of the total 15 patients, the number of patients in group A, B, and C were 8, 4, and 3, respectively. SRY gene was positive in all group A and B patients but only one patient was positive in group C. Of the 8 patients in group A, 5 patients had a high XY mosaicism ratio compared to XO whereas an equal ratio was observed in the remaining 3 patients. Of the 4 male penotype patients only 1 patient had a high XY mosaicism ratio compared to XO while 3 patients displayed an equal ratio. There was no difference in associated anomaly and the degree of severity of ambiguity according to the mosaicism ratio in all patients. CONCLUSIONS: There was no definite correlation between the mosaicism ratio and phenotypic expression. Presence of SRY gene in 45XO patients may suggest MGD(mixed gonadal dysgenesis) and therefore, the evaluation SRY gene could be useful in the diagnosis of 45XO patients with ambiguous genitalia.
Chromosome Aberrations ; Diagnosis ; Disorders of Sex Development ; Genes, sry* ; Gonadal Dysgenesis, Mixed ; Gonads ; Humans ; Male ; Mosaicism*

BACKGROUND: Microdeletion syndromes not detectable by conventional cytogenetic analysis have been reported to occur in approximately 5% of patients with unexplained mental retardation (MR). Therefore, it is essential to ensure that patients with MR are screened for these microdeletion syndromes. Mental retardation syndrome multiplex ligation-dependent probe amplification (MRS-MLPA) is a new technique for measuring sequence dosages that allows for the detection of copy number changes of several microdeletion syndromes (1p36 deletion syndrome, Williams syndrome, Smith-Magenis syndrome, Miller-Dieker syndrome, DiGeorge syndrome, Prader-Willi/Angelman syndrome, Alagille syndrome, Saethre-Chotzen syndrome, and Sotos syndrome) to be processed simultaneously, thus significantly reducing the amount of laboratory work. METHODS: We assessed the performance of MLPA (MRC-Holland, The Netherlands) for the detection of microdeletion syndromes by comparing the results with those generated using FISH assays. MLPA analysis was carried out on 12 patients with microdeletion confirmed by FISH (three DiGeorge syndrome, four Williams syndrome, four Prader-Willi syndrome, and one Miller-Dieker syndrome). RESULTS: The results of MLPA analysis showed a complete concordance with FISH in 12 patients with microdeletion syndromes. CONCLUSIONS: On the basis of these results, we conclude that MLPA is an accurate, reliable, and cost-effective alternative to FISH in the screening for microdeletion syndromes.
*Chromosome Deletion ; Classical Lissencephalies and Subcortical Band Heterotopias/genetics ; DiGeorge Syndrome/genetics ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Laboratories, Hospital ; Mental Retardation/*diagnosis/genetics ; Nucleic Acid Amplification Techniques/*methods ; Prader-Willi Syndrome/genetics ; Williams Syndrome/genetics