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Holoprosencephaly (HPE) is genetically heterogeneous. Variable phenotypic manifestations within families with normal and affected patients have been attributed to the number and type of HPE gene mutations. Environmental agents may also contribute to the severity as well as the requirement of multiple hits. Clinical expression is extremely variable ranging from minor facial signs to complex craniofacial anomalies such as cyclopia. Main genes involved include SHH, GLI2, PTCH1, TGIF, ZIC2, TDGF1, SIX3; however, several other candidates have been proposed. Recently it was established that the human growth arrest specific gene 1 (GAS1) is a potential locus for several human craniofacial malformations. Here, we report on four Brazilian patients with GAS1 DNA sequence change who presented variable phenotypical manifestations ranging from classic HPE to HPE-like signs. Two patients had single DNA sequence change in the GAS1 gene, while in other two, an additional mutation in the SHH gene was observed. Clinical manifestations presented by these patients suggest that GAS1 could be considered a candidate locus for one of the types of human HPE., ((c) 2010 Wiley-Liss, Inc.)

Human neutrophil reactive antibodies may cause clinical disorders such as transfusion-related acute lung injury, febrile transfusion reactions, alloimmune neonatal neutropenia, immune neutropenia after stem cell transplantation, refractoriness to granulocyte transfusion, drug-induced neutropenia and autoimmune neutropenia. Using the granulocyte immunofluorescence test by flow cytometry, the phenotypic frequencies of the human neutrophil alloantigens (HNA)-1a, -1b, -2, -3a and -4a were determined in 100 healthy Brazilian persons. Neutrophils were separated from blood samples by sedimentation, centrifugated and incubated with HNA-specific alloantibody plus fluorescein isothiocyanate-labeled F(ab')(2) fragments of anti-human IgG. The results showed that the phenotype frequencies of HNA-1a, -1b, -2a, -3a and -4a were 65%, 83%, 97%, 95% and 94%, respectively. We detected that neutrophils from 17% of Brazilians typed positive only with anti-HNA-1a (HNA-1a/a), 35% only with anti-HNA-1b (HNA-1b/b) and 48% reacted with both antibodies (HNA-1a/b). The frequencies found for HNA-1a and -1b were quite similar to that reported among Africans and American-Africans, but different from those found in Japanese and Chinese. In addition, our data showed that the frequencies of HNA-2, -3a and -4a in Brazilians were comparable with those observed in Caucasians. The determination of HNAs frequencies among populations with distinct racial backgrounds is important not only for anthropological reasons, but also for neonatal typing in suspected cases of alloimmune neutropenia or when patients are severely neutropenic.

Background: Polymorphisms in FcgammaR have been associated with different forms of periodontitis. This study determined the frequency of FcgammaRIIa and FcgammaRIIIb alleles/genotypes in patients with generalized aggressive periodontitis (GAgP)., Methods: Thirty-one GAgP and 49 periodontally healthy Brazilian subjects participated in the study. Full-mouth periodontal examinations were carried out, and mouthwash samples were collected for human DNA isolation. FcgammaR genotyping was performed by polymerase chain reaction and hybridization with allele-specific oligonucleotide probes. Significant differences between groups were sought by Mann-Whitney, chi2, and Fisher exact tests and configural frequency analysis., Results: FcgammaRIIa-H131 (53.8%) and FcgammaRIIIb-NA1 (75%) were the most prevalent alleles in this sample population. A significant overrepresentation of FcgammaRIIIb-NA2 was observed in the GAgP group, whereas FcgammaRIIIb-NA1 was detected more often in healthy individuals (odds ratio, 32.5; 95% confidence interval [CI], 10.6 to 99.8; P<0.001). No significant differences in the distribution of the FcgammaRIIa genotypes were observed between the groups. The prevalence of FcgammaRIIIb-NA2/NA2 was higher in GAgP patients, whereas FcgammaRIIIb-NA1/NA1 was predominant in the healthy group (chi2=45.1; P<0.001). The combination of the genotypes FcgammaRIIIb-NA2/NA2 plus FcgammaRIIa-H/H131 was observed more frequently in GAgP subjects than expected from marginal frequencies (chi2=12.5; P<0.001)., Conclusions: The data suggest that the FcgammaRIIIb-NA2 allele and/or FcgammaRIIIb-NA2/NA2 genotype and the composite genotype FcgammaRIIIb-NA2/NA2 plus FcgammaRIIa-H/H131 may be associated with GAgP, whereas FcgammaRIIIb-NA1 and/or FcgammaRIIIb-NA1/NA1 may be related to periodontal health in this sample of the Brazilian population.

The FCGR3B gene codes for the FcgammaR3b receptor, which occurs in three polymorphic forms representing the human neutrophil antigens (HNA)-1a, HNA-1b, and HNA-1c. The alleles that code for these antigens are FCGR3B*1, FCGR3B*2, and FCGR3B*3, respectively. New variants of these alleles have been recently described. In order to study the frequency of these alleles and the occurrence of variant forms, we sequenced part of the FCGR3B gene in 149 individuals belonging to four distinct Brazilian populations, i.e., 60 Amerindians, 30 Whites of European descent, 30 Afro-Brazilians, and 30 Japanese. The FCGR3B*1 allele showed high frequency among Amerindians (0.850), with the value detected representing the highest frequency described thus far for this allele in population studies. Its frequency was 0.660 in the Japanese population studied, a value equal to that observed in Afro-Brazilians (0.600) and higher than that observed in Whites (0.480). The FCGR3B*3 allele was only found among Afro-Brazilians, where it occurred at a frequency of 0.080, which was lower than the frequency observed among Afro-North Americans (0.207) and Ugandans (0.166). Two variant haplotypes were detected among Amerindians and Afro-Brazilians, occurring in six individuals (four Amerindians and two Afro-Brazilians). The variant haplotype FCGR3B*1 A227G, which occurred in homozygosis in two Amerindians and in heterozygosis in two Afro-Brazilians, is described for the first time in the present report. In general, these data reveal variability in the frequency of alleles of the FCGR3B gene compared to other populations of the same genetic background in other regions of the world.

The HPA-15 (Gov) alloantigen is a biallelic co-dominant system on human platelets, and its allele HPA-15a and HPA-15b differ by an A-->C single nucleotide polymorphism at nucleotide 2108 of the coding sequence resulting in a Tyr682Ser substitution in the mature CD109 glycoprotein. Employing the polymerase chain reaction-restriction fragment length polymorphism technique, we determined the HPA-15 gene frequencies among 276 subjects of distinct Brazilian ethnic groups including, 15 Caucasians, 15 African Brazilians, 15 Orientals, 106 Amazon Xikrin Indians, 31 Amazon Gavioes Indians and 94 blood donors. The calculated HPA-15a and HPA-15b allele frequencies found in Caucasians (0.53/0.47), African Brazilians (0.57/0.43), Orientals (0.57/0.43) and Brazilian blood donors (0.52/0.48) did not differ significantly. However, the HPA-15a and HPA-15b gene frequencies of Xikrin Indians (0.78/0.22) were significantly different from that of all other groups (P < 0.01). The HPA-15a/a, HPA-15a/b and HPA-15b/b genotype frequencies observed in Gavioes Indians were significantly different from those seen in African Brazilians (P = 0.04) and blood donors (P = 0.017). The present data showed that the distribution of the HPA-15 (Gov) system alleles observed among the Brazilian population is quite similar to the distributions already reported among Asian, Canadian and European populations. Moreover, the data indicated differences in the frequency of the HPA-15 system between Amazon Indians and other distinct Brazilian ethnic groups suggesting that Amerindians would be at higher risk of HPA-15 alloimmunization in the need of receiving blood components collected from blood donors of other ethnic groups.

The identification of a null allele in a human genetic system restricted to the placenta is a great challenge for two reasons: the impossibility of carrying out family studies and the unviability of sample recollections because the placenta itself is a disposable universe. Thus, in addition to reporting the finding of a null phenotype of placental alkaline phosphatase in a dark mulatto newborn from a black mixed population of Bahia, Brazil, here we present other evidence for the presence of the ALPP*Q0 allele with considerably high frequency in this population.