[Familiar case of granular dystrophy and oculocutaneous albinism]. / Asociación de albinismo oculocutáneo y distrofia granular en una familia.

CLINICAL CASE: A 35-year-old female patient with blurred vision since childhood, for which no treatment had been given, presented with poor visual acuity. She had white skin and fair yellow hair. There were several well circumscribed deposits in the central and anterior corneal stroma, and iris transillumination and foveal hypoplasia were evident. The clinical diagnosis was oculo-cutaneous albinism and granular corneal dystrophy. We found oculo-cutaneous albinism in two brothers and granular dystrophy in three brothers, the mother and a son. DISCUSSION: Corneal dystrophy is an autosomal dominant disorder inherited independently of oculocutaneous albinism, which is inherited as an autosomal recessive condition. This is the first case report of granular dystrophy concurrent with oculocutaneous albinism.

Asociación de albinismo oculocutáneo y distrofia granular en una familia / Familiar case of granular dystrophy and oculocutaneous albinism

Caso clínico: Paciente femenino de 35 años deedad con mala agudeza visual desde la infancia. Ala exploración se encontró baja agudeza visual, nistagmo,hipopigmentación de piel y cabello amarillento,córnea con depósitos blanquecinos en estromacentral y anterior, transiluminación de iris ehipoplasia foveal. Se diagnosticaron albinismo oculocutáneoy distrofia corneal granular. Se encontróalbinismo oculocutáneo en dos hermanos y distrofiagranular en tres hermanos, la madre y el hijo.Discusión: La distrofia corneal granular se transmitegenéticamente siguiendo un patrón autosómicodominante e independiente del albinismo oculocutáneo.Este es el primer caso publicado de presentaciónconcomitante de ambas entidades

Clinical case: A 35-year-old female patient with ;;blurred vision since childhood, for which no treatment ;;had been given, presented with poor visual ;;acuity. She had white skin and fair yellow hair. There ;;were several well circumscribed deposits in the ;;central and anterior corneal stroma, and iris transillumination ;;and foveal hypoplasia were evident. ;;The clinical diagnosis was oculo-cutaneous albinism ;;and granular corneal dystrophy. We found oculo- ;;cutaneous albinism in two brothers and granular ;;dystrophy in three brothers, the mother and a son. ;;Discussion: Corneal dystrophy is an autosomal ;;dominant disorder inherited independently of oculocutaneous ;;albinism, which is inherited as an autosomal ;;recessive condition. This is the first case ;;report of granular dystrophy concurrent with oculocutaneous ;;albinism

Ancestral RET haplotype associated with Hirschsprung's disease shows linkage disequilibrium breakpoint at -1249.

BACKGROUND: Hirschsprung disease (HSCR) is a complex disorder with traditional germline mutations in RET in up to 30% of familial cases and in 3% of sporadic cases in a population-based series. We have previously demonstrated that an ancestral haplotype at the 5' end of RET (haplotype 0) was strongly associated with a large subset of isolated HSCR cases and that a putative low penetrance susceptibility locus was encompassed within this ancestral haplotype, anchored by exon 2 SNP A45A. OBJECTIVE: To determine the 5' extent of the HSCR-associated ancestral haplotype by defining the linkage disequilibrium breakpoint in search for the low penetrance susceptibility locus. METHODS: Systematic screening of the region upstream of the anchoring A45A SNP, comprising RET intron 1, exon 1, and promoter in 117 population-based HSCR cases and 100 controls. Dual luciferase assay to determine differential activities between SNP combinations near a transcription start site. RESULTS: New SNP's were found which formed upstream haplotypes, anchored by A45A, in linkage disequilibrium with HSCR (2 = 76.96, p<0.00000001). Linkage disequilibrium appeared to break at the -1249C/T SNP. Further, the HSCR-associated genotype (00) was found in >60% of HSCR but only 2% of controls. Because only 2 variants, -200A>G and -196C>A, lie within the promoter region and are in proximity to the transcriptional start site (at -195), we modelled these combinations into constructs for luciferase reporter assay. The HSCR-associated SNP combination showed the lowest activity and the control-associated combination, the highest. CONCLUSIONS: Our observations seem to discard the existence of a HSCR-causing mutation as it is conceived in the traditional sense, but strengthen the idea of a specific combination of variants conferring susceptibility to the disease in a low penetrance fashion. The data derived from our functional "in vitro" studies would suggest that the HSCR-associated haplotype 0 may result in a lower level of expression of the RET gene [corrected]

Cloning and expression of the algL gene, encoding the Azotobacter chroococcum alginate lyase: purification and characterization of the enzyme.

The alginate lyase-encoding gene (algL) of Azotobacter chroococcum was localized to a 3.1-kb EcoRI DNA fragment that revealed an open reading frame of 1,116 bp. This open reading frame encodes a protein of 42.98 kDa, in agreement with the value previously reported by us for this protein. The deduced protein has a potential N-terminal signal peptide that is consistent with its proposed periplasmic location. The analysis of the deduced amino acid sequence indicated that the gene sequence has a high homology (90% identity) to the Azotobacter vinelandii gene sequence, which has very recently been deposited in the GenBank database, and that it has 64% identity to the Pseudomonas aeruginosa gene sequence but that it has rather low homology (15 to 22% identity) to the gene sequences encoding alginate lyase in other bacteria. The A. chroococcum AlgL protein was overproduced in Escherichia coli and purified to electrophoretic homogeneity in a two-step chromatography procedure on hydroxyapatite and phenyl-Sepharose. The kinetic and molecular parameters of the recombinant alginate lyase are similar to those found for the native enzyme.

A sensor protein involved in induction of nitrate assimilation in Azotobacter chroococcum.

Nitrogen-fixing Azotobacter chroococcum cells, but not ammonium- or nitrate-grown cells, exhibited two polypeptide components of 22 and 35 kDa, respectively, that we termed P22 and P35. Bidimensional polyacrylamide gel electrophoresis analysis of preparations from N2-fixing cells that had been transferred to nitrate medium and then incubated for 2 h revealed that P22 had shifted to a more acidic part of the gel while P35 did not change its electrophoretic pattern. Using [32P]orthophosphoric acid it could be demonstrated that the shift in mobility of P22 was due to the phosphorylation of the polypeptide dependent on nitrate (nitrite). The A. chroococcum TR1 strain, which is unable to use nitrate as a nitrogen source and displays activities of nitrogenase, nitrate reductase and nitrite reductase, exhibited both polypeptides. In contrast, P22 and P35 were absent from A. chroococcum MCD1, a mutant strain that cannot assimilate nitrate and lacks the nitrate-reducing enzymatic system. The results suggest that P22 could act as a sensor protein for nitrate in A. chroococcum.

Detection of alginate lyase by activity staining after sodium dodecil sulfate-polyacrylamide gel electrophoresis and subsequent renaturation.

A slab gel electrophoretic method for the study of bacterial alginate lyase has been developed. By incorporating alginate in acrylamide gels, the method is based on renaturation of the enzyme after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, subsequent staining with cetylpyridinium chloride, and quantification of the spot by densitometric scanning. The molecular mass of alginate lyase can be determined from its position in the gel.