Two cases of Fanconi-Bickel syndrome: first report from China with novel mutations of SLC2A2 gene.

Fanconi-Bickel syndrome (FBS) is a rare inherited disease caused by mutations in the glucose transporter 2 gene, SLC2A2. We reported the first two Chinese cases of FBS. Both cases presented typical clinical features of hepatomegaly, hypophosphatemic rickets, severely stunted growth, fasting hypoglycemia along with postprandial hyperglycemia, and proximal renal tubular dysfunction with disproportionately severe glucosuria. Genetic analysis of SLC2A2 gene revealed novel compound heterozygous mutations in both patients. The characteristics of being born as small for gestational age and apparent liver dysfunction in our cases have been seldom discussed in the literature. It seems FBS patients in general have lower birth weight than normal, but further data collection is still needed. Symptomatic treatments were effective, but the serum transaminase of patient 2 remained moderately increased, and he patient needed further follow-up. The present study will supplement the up-to-date clinical characteristic spectrum for FBS.

Detection of α-globin gene deletion and duplication using quantitative multiplex PCR of short fluorescent fragments.

BACKGROUND: The aim of this study was to establish a sensitive method that can detect the presence of not only the common but also the unusual or unknown α-globin gene deletions for screening of α-thalassemia. We used quantitative multiplex PCR of short fluorescent fragments (QMPSF) for the α-globin genes (HBA) to screen α-thalassemia deletions. METHODS: We set up and validated HBA-QMPSF using 50 negative and 100 positive controls of deletional α-thalassemia. To evaluate its ability to detect the presence of the common and unusual or unknown α-globin gene deletions, 579 unrelated samples were simultaneously analyzed using this assay and multiplex Gap polymerase chain reaction (Gap-PCR). The inconsistent results were further confirmed by multiplex ligation-dependent probe amplification (MLPA). RESULTS: HBA-QMPSF was capable of detecting α-globin gene deletions with an acceptable variability as shown by mean values (SD) of allele dosage for the heterozygous deleted control obtained from intra- and inter-experimental replicates [0.63 (0.01) and 0.61 (0.03)]. In 572 out of the 579 unrelated subjects, HBA-QMPSF and multiplex Gap-PCR gave consistent results. In seven cases which were finally proved to be composed of one rare deletion--Thai/-α3.7, one novel deletion--SEA/-α2.8, four αααanti3.7/αα and one αααanti4.2/αα triplications, HBA-QMPSF showed deletion or duplication in the α-globin gene while multiplex Gap-PCR failed to give the correct diagnosis. CONCLUSIONS: HBA-QMPSF is able to detect the presence of the common and unusual or unknown α-thalassemia deletions and duplications. It can be used as an initial screening test for α-thalassemia caused by HBA gene copy number alteration.

[Screening of proteins binding to FXR1P using yeast two-hybrid technique].

OBJECTIVE: To screen the proteins interacting with FXR1P for functional investigation of FXR1P. METHODS: The yeast strain AH109 transformed with the recombinant expression vector pGBKT7/FXR1 was mated with the yeast strain Y187 pretransformed with human fetal brain cDNA library. The positive clones were screened and identified by sequence analysis. RESULTS: The recombinant expression vector pGBKT7/FXR1 was constructed successfully. Five proteins binding to FXR1P were screened from human fetal brain cDNA library using the yeast two-hybrid system, including CMAS, FTH1, GOLGA4, HSD17B1 and CSH1. CONCLUSIONS: These results provide new clues for investigating the biological functions of FXR1P and the pathogenesis of Fragile X syndrome.

[Polymorphism of DXS15, CA13, CA22 loci in Guangdong normal population].

The aim of this study was to investigate the polymorphism of microsatellite repeats DXS15, CA13, CA22 tightly linked to FVIII gene in Guangdong population and its practical value in genetic diagnosis for hemophilia A. The polymerase chain reaction (PCR) and capillary electrophoresis (CE) methods were adopted to test the variability of the 3 microsatellite repeat in Guangdong females, including 111 females, 222 X chromosomes for detecting DXS15 polymorphism; 87 females, 174X chromosomes for detecting CA13 polymorphism; 94 females, 188 X chromosomes for detecting CA22 polymorphism. The results indicated that 11 alleles corresponding to DXS15 were found at this locus with size ranging from 140 to 160 bp. The polymorphism information content (PIC) of this microsatellite repeat was 0.82, heterozygosity was 82%. Six alleles corresponding to CA13 were found, with a size from 145 to 155 bp, and PIC was 0.56, heterozygosity was 56.2%. Four alleles corresponding to CA22 were found with size ranging from 79 to 85 bp, and PIC was 0.41, heterozygosity was 50%. It is concluded that in contrast to the information about Caucasian, the polymorphism of these 3 microsatellites differs from race to race, and region to region. DXS15, CA13 and CA22 are highly polymorphic genetic markers useful for linkage analysis of haemophilia A, which may play a vital role in detection and prenatal diagnosis for hemophilia A.