OBJECTIVE: Using molecular techniques, we typed 2 short tandem repeat (STR) loci on 21 chromosome to establish the method for rapid and accurate diagnosis of trisomy 21. METHODS: Genomic DNA samples from 50 individuals diagnosed previously by karyotype as trisomy 21 and 40 children with severe mental retardation (IQ < 50) suspected of trisomy 21 were analyzed for 2 short tandem repeat loci on 21 chromosome, D21S1435 and D21S2055. Typing was carried out after polymerase chain reaction (PCR) and silver staining. The trisomy was identified by the number of alleles: 3 alleles bands whose density is same, two alleles bands with one obvious higher density compared to the other and one allele band whose density is three times than the normal control. RESULTS: All of the complete trisomy 21 were detected by this method; the parental source was easily determined. CONCLUSION: This method for diagnosing trisomy 21 is rapid and accurate.

J Pediatr. 2002 Dec;141(6):804-10.
The impact of early cystic fibrosis diagnosis on pulmonary function in children.
Wang SS, O'Leary LA, Fitzsimmons SC, Khoury MJ.
Office of Genetics and Disease Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

OBJECTIVE: To investigate the impact of early diagnosis on pulmonary function in a large cohort of children with cystic fibrosis (CF). STUDY DESIGN: CF cases identified from the CF Foundation National Patient Registry and diagnosed between 1982 and 1990 were categorized as: early asymptomatic diagnosis (EAD; n = 157), early symptomatic diagnosis (ESD; n = 227), later asymptomatic diagnosis (LAD; n = 161), and later symptomatic diagnosis (LSD; n = 3080). Early CF diagnosis was diagnosis before 6 weeks of age; later diagnosis was diagnosis at 6 weeks to 36 months of age, inclusive. Asymptomatic diagnosis included diagnosis by either family history, genotype, prenatally, or neonatally. Pulmonary function was measured as percentage of predicted forced expiratory volume in one second (FEV(1)). RESULTS: There were no overall differences in pulmonary function among the 4 diagnostic groups. However, EAD cases born more recently (1987 or later) had a higher mean FEV(1) throughout the study, compared with the remaining diagnostic groups. For this later birth cohort, Cox regression analysis for those diagnosed later and/or symptomatically, demonstrated a 2-fold increase in risk (P =.06) for having moderate-to-severe pulmonary function (FEV(1) <70%) at ages 6 to 10 years, compared with EAD cases. CONCLUSIONS: Children diagnosed with CF early, asymptomatically and more recently may have better pulmonary function throughout early childhood, probably as a result of improved CF treatments in recent years.

Zhonghua Xue Ye Xue Za Zhi. 2002 Jun;23(6):307-10.
A preliminary study on the early diagnosis of myelodysplastic syndromes.
Qian J, Xue Y, Yu F, Wu Y, Pan J, Lu D.
First Affiliated Hospital, Soochow University, Jiangsu Institute of Hematology, Suzhou 215006, China.

OBJECTIVE: To evaluate the four techniques for clonal analysis in the early diagnosis of myelodysplastic syndromes (MDS). METHODS: Four techniques for clonal analysis were performed in bone marrow samples from fifty patients with suspected MDS: (1) Conventional cytogenetics (CC) for clonal chromosomal abnormalities; (2) BrdU-sister chromatid differentiation (BrdU-SCD) for cell cycle analysis; (3) Fluorescence in situ hybridization (FISH) for trisomy 8; (4) PCR-SSCP for N-ras mutation. RESULTS: The diagnosis of forty-five patients was compatible with FAB criteria of MDS, the other five patients didn't fully meet the FAB criteria. They had either only one lineage dyspoiesis or no any obvious dysplastic features and two of them were diagnosed as suspicious refractory anemia (RA), one as anemia with hypercellular bone marrow and two as chronic aplastic anemia. The results of the four techniques performed in them showed that four patients had clonal karyotype abnormalities, two had prolonged cell cycle, three had trisomy 8 of different proportions, and one had N-ras mutation. Thus, they were all diagnosed as RA. CONCLUSION: The untypical MDS patients can be diagnosed early by examination with combining several clonal analysis techniques.

SADJ. 2001 May;56(5):242-5.
Gardner's syndrome--the importance of early diagnosis: a case report and a review.
Buch B, Noffke C, de Kock S.
Department of Diagnostics and Rontgenology, University of Pretoria, PO Box 1266, Pretoria 0001.

Gardner's syndrome (familial polyposis coli) is a genetic condition characterised by colonic polyps that carry a 100% risk of malignancy if untreated. Early diagnosis, in which an astute and knowledgeable dentist can play an essential role, is therefore of paramount importance. The presence of multiple unerupted teeth provides the dentist with a major pointer to the possible presence of this disease, which may be provisionally diagnosed on the detection of two other obvious features, namely osteomas and cutaneous lesions. This fact is clearly illustrated by the accompanying case report. Extracolonic manifestations increase the morbidity and make treatment more difficult. The presence of large desmoid tumours may be a serious complicating factor. Gardner's syndrome may be accompanied by adenomas of the stomach and duodenum and very rarely by malignant tumours of the central nervous system. Regular surveillance by means of colonoscopies must be carried out on all individuals suspected of having the disease in order to implement timeous life-saving prophylaxis.

Pediatrics. 2001 Jan;107(1):1-13.
Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. Wisconsin Cystic Fibrosis Neonatal Screening Study Group.
Farrell PM, Kosorok MR, Rock MJ, Laxova A, Zeng L, Lai HC, Hoffman G, Laessig RH, Splaingard ML.
University of Wisconsin Medical School, Madison, Wisconsin, USA.

OBJECTIVE: Despite its relative frequency among autosomal recessive diseases and the availability of the sweat test, cystic fibrosis (CF) has been difficult to diagnose in early childhood, and delays can lead to severe malnutrition, lung disease, or even death. The Wisconsin CF Neonatal Screening Project was designed as a randomized clinical trial to assess the benefits and risks of early diagnosis through screening. In addition, the incidence of CF was determined, and the validity of our randomization method assessed by comparing 16 demographic variables. METHODOLOGY: Immunoreactive trypsinogen analysis was applied to dried newborn blood specimens for recognition of CF risk from 1985 to 1991 and was coupled to DNA-based detection of the DeltaF508 mutation from 1991 to 1994. Randomization of 650 341 newborns occurred when their blood specimens reached the Wisconsin screening laboratory. This created 2 groups-an early diagnosis, screened cohort and a standard diagnosis or control group. To avoid selection bias, we devised a unique unblinding method with a surveillance program to completely identify the control subjects. Because sequential analysis of nutritional outcome measures revealed significantly better growth in screened patients during 1996, we accelerated the unblinding and completely identified the control group by April 1998. Having each member of this cohort enrolled and evaluated for at least 1 year and having completed a comprehensive surveillance program, we performed another statistical analysis of anthropometric evaluated indices that includes all CF patients without meconium ileus. RESULTS: The incidence of classical CF, ie, patients diagnosed in this trial with a sweat chloride of 60 mEq/L greater, was 1:4189. By incorporating other CF patients born during the randomization period, including 2 autopsy diagnosed patients and 8 probable patients, we calculate a maximum incidence of 1:3938 (95% confidence interval: 3402-4611). Although there were group differences in the proportion of patients with DeltaF508 genotypes and with pancreatic insufficiency, validity of the randomization plan was demonstrated by analyzing 16 demographic variables and finding no significant difference after adjustment for multiple comparisons. Focusing on patients without meconium ileus, we found a marked difference in the mean +/- standard deviation age of diagnosis for screened patients (13 +/- 37 weeks), compared with the standard diagnosis group (100 +/- 117). Anthropometric indices of nutritional status were significantly higher at diagnosis in the screened group, including length/height, weight, and head circumference. During 13 years of study, despite similar nutritional therapy and the inherently better pancreatic status of the control group, analysis of nutritional outcomes revealed significantly greater growth associated with early diagnosis. Most impressively, the screened group had a much lower proportion of patients with weight and height data below the 10th percentile throughout childhood. CONCLUSIONS: Although the screened group had a higher proportion of patients with pancreatic insufficiency, their growth indices were significantly better than those of the control group during the 13-year follow-up evaluation and, therefore, this randomized clinical trial of early CF diagnosis must be interpreted as unequivocally positive. Our conclusions did not change when the height and weight data before 4 years of age for the controls detected by unblinding were included in the analysis. Also, comparison of growth outcomes after 4 years of age in all subjects showed persistence of the significant differences. Therefore, selection bias has been eliminated as a potential explanation. In addition, the results show that severe malnutrition persists after delayed diagnosis of CF and that catch-up may not be possible. We conclude that early diagnosis of CF through neonatal screening combined with aggressive nutritional therapy can result.

Prenat Diagn. 1991 Jan;11(1):41-6.
Extraction of DNA from amniotic fluid cells for the early prenatal diagnosis of genetic disease.
Rebello MT, Hackett G, Smith J, Loeffler FE, Robson S, MacLachlan N, Beard RW, Rodeck CH, Williamson R, Coleman DV, et al.
Department of Cytogenetics, St Mary's Hospital, Paddington, London, U.K.

Ten-ml samples of amniotic fluid were taken from pregnancies being terminated at 8-14 weeks' gestation. DNA was extracted from the amniotic cells by sequential centrifugation and analysed using the polymerase chain reaction (PCR). Fifteen samples were analysed for evidence of maternal contamination using Mfd5 oligonucleotide primers for repeat polymorphisms. Ten amniotic fluid samples were tested for the Delta-F508 deletion characteristic of cystic fibrosis to demonstrate a diagnostic application for the technique. In each case, DNA extracted from fetal tissue from the same pregnancy was included in the controls. In 14 of the 15 cases tested with the Mfd5 primers, both the amniotic fluid DNA and the fetal DNA showed no evidence of contaminating DNA. In one case, neither the amniotic fluid cells nor the fetal cells yielded results. In nine of the ten cases tested with the Delta-F508 primers, the amniotic fluid cell DNA provided accurate information about the genetic status of the fetus; in the tenth, the fetal DNA failed to amplify. The results indicate that adequate DNA can be extracted from amniotic fluid from 8 weeks' gestation onward and these samples are suitable for prenatal diagnosis using PCR.

J Reprod Med. 1988 May;33(5):450-2.
Early genetic amniocentesis and chorionic villus sampling. Expanding the opportunities for early prenatal diagnosis.
Evans MI, Koppich FC 3rd, Nemitz B, Quigg MH, Zador IE.
Department of Obstetrics and Gynecology, Hutzel Hospital/Wayne State University, Detroit, MI 48201.

At centers where chorionic villus sampling (CVS) programs are operational, first-trimester prenatal diagnosis has been shown to have many advantages, both medical and psychologic. However, most medical centers do not have CVS capability, nor are all patients candidates for CVS. We investigated the feasibility of performing very early genetic amniocentesis (9-13 weeks' gestational age). The results from those amniocenteses were compared to our own CVS data. In experienced hands, (1) CVS can be performed safely at 8-13 weeks, with the most technical ease at 9-11 weeks; (2) CVS or amniocentesis can be performed on many patients at 12-13 weeks or perhaps even earlier, although no accurate loss rates are available yet; (3) when technically feasible, CVS may be advantageous because of the much faster time period for cytogenetic results from direct preparation or short-term culture; and (4) in those patients on whom CVS cannot be performed, early amniocentesis in selected patients may offer the benefits of early diagnosis.