No abstract

If carrier women could be identified in time and take appropriate measures, fragile X syndrome (FXS) can be prevented. Wide screening of women to be or in their early pregnancy was considered a good approach to identify carriers without misdetection. Nevertheless, we argued against the cost-effectiveness of implementing such a screening program in Taiwan, due to the lower carrier rate found in our pilot study. To reliably estimate the prevalence of mutant FMR1 gene in Taiwan, we anonymously screened 10,046 newborn boys using bloodspot polymerase chain reaction (PCR). Among them, the sample from one boy, who was most likely had FXS, failed repeatedly in PCR amplification. The estimated prevalence of premutation (55-200 CGG repeats) and intermediate alleles (45-54 CGG repeats) was 1:1,674 (n = 6) and 1:143 (n = 70), respectively. All these estimates were constantly lower than that reported in Caucasian populations, with variable statistic significance. Furthermore, when comparing analyses of the distribution of alleles at the two most often investigated microsatellite loci, DXS548 and FRAXAC1, between 100 control and 28 unrelated fragile X chromosomes, we found no apparent founder haplotype prevalent among the fragile X patients. Because a few founder haplotypes were reportedly prevalent in two thirds of fragile X alleles in Caucasians and in Chinese from Central China, we thus suggested that lack of founder fragile X chromosomes might result in a relatively low prevalence of mutant FMR1 gene in a population, as observed in Taiwan.

Although congenital mesoblastic nephroma (CMN) is a rare benign congenital renal tumor, it is the most common solid renal tumor in the newborn period. The most common presentation of congenital mesoblastic nephroma is polyhydramnios, and only one case with prenatal fetal hydrops has been previously reported. Prenatal diagnosis of CMN has previously been made on the basis of the findings of sonography in the third trimester, and magnetic resonance imaging (MRI)-based diagnosis has been reported recently. Here we report a case of prenatally diagnosed classical type CMN diagnosed at 22 + 3 weeks of gestation based on the findings of sonography and magnetic resonance imaging. The characteristic imaging findings in this case were fetal hydrops and polyhydramnios. To our knowledge, this is the youngest reported gestational age for prenatal diagnosis of CMN and it is the second case of CMN associated with fetal hydrops detected prenatally.

No abstract

Purpose: Chromosome 9 is frequently deleted in high-risk gastrointestinal stromal tumors (GISTs), whereas its specific tumor suppressor genes (TSGs) are less understood. We did an integrative study of MTAP gene at 9p21 to analyze its implication in GISTs. Experimental Design: To search TSGs on chromosome 9, we used ultrahigh-resolution array comparative genomic hybridization to profile DNA copy number alterations of 22 GISTs, with special attention to MTAP gene. MTAP immunoexpression was assessable for 306 independent GISTs on tissue microarrays, with 146 cases analyzed for MTAP homozygous deletion, 181 for mutations of KIT and PDGFRA receptor tyrosine kinase genes, and 7 for MTAP hypermethylation. Results: Array comparative genomic hybridization identified 11 candidate TSGs on 9p and six on 9q. MTAP and/or CDKN2A/CDKN2B at 9p21.3 were deleted in one intermediate-risk (11%) and seven high-risk (70%) GISTs with two cases homozygously codeleted at both loci. MTAP homozygous deletion, present in 25 of 146 cases, was highly associated with larger size and higher mitotic rate, Ki-67 index, and risk level (all P < 0.01) but not with receptor tyrosine kinase genotypes. Whereas MTAP homozygous deletion correlated with MTAP protein loss (P < 0.001), 7 of 30 GISTs without MTAP expression did not show homozygous deletion, including three MTAP-hypermethylated cases. MTAP homozygous deletion was univariately predictive of decreased disease-free survival (P < 0.0001) and remained multivariately independent (P = 0.0369, hazard ratio = 2.166), together with high-risk category (P < 0.0001), Ki-67 index >5% (P = 0.0106), and nongastric location (P = 0.0416). Conclusions: MTAP homozygous deletion, the predominant mechanism to deplete protein expression, is present in 17% of GISTs. It correlates with important prognosticators and independently predicts worse outcomes, highlighting the role in disease progression. (Clin Cancer Res 2009;15(22):6963-72)