The phenotype of Type I OCA is broad, ranging from a total lack to only a moderate reduction of melanin, and the phenotypic variation is associated with different mutant alleles at the tyrosinase locus.
Tyrosinase is a rate-limiting enzyme in the melanin biosynthetic pathway and a complete defect of the enzyme activity caused by homozygous mutations of the tyrosinase gene is well known to result in tyrosinase-negative oculocutaneous albinism (OCA1A) patients who never develop any melanin pigment in the skin, hair and eyes throughout life.
Sequence-based diagnosis of tyrosinase-related oculocutaneous albinism: successful sequence analysis of the tyrosinase gene from blood spots dried on filter paper.
The third, termed ts, produces temperature-sensitive tyrosinase with very low activity at 35 degrees C, but with no activity at temperatures greater than 35 degrees C. Various combinations of these alleles result in tyrosinase-negative (t-/t-), yellow mutant (y/y, y/t-, y/ts), or temperature-sensitive (ts/t-, ts/ts) OCA.
Mutations T373K, N371Y, M370T and P313R were suggested as high deleterious effect on TYR protein and it is responsible for OCA1A which were also endorsed with previous in vivo experimental studies.
The recent elucidation of the specific gene mutation of tyrosinase in the affected individuals now allows the DNA-based prenatal diagnosis of tyrosinase-negative oculocutaneous albinism in the first trimester of pregnancy.
Using the full-length cDNA encoding human tyrosinase and its exon-specific fragments as hybridization probes, we show that overall structural organization of the tyrosinase gene is unchanged in three patients affected with tyrosinase-negative oculocutaneous albinism (OCA).
We then analyzed new patients affected with tyrosinase-negative OCA, and based the diagnosis on both the results of a clinical examination and those of a hair bulb test using ASA with the modified allele-specific primers.
Direct DNA sequence determination of PCR amplified exons of the tyrosinase gene of three British patients suffering from tyrosinase negative oculocutaneous albinism has revealed three new missense point mutations: (1) an adenine to guanine transition at codon 1 changes the initiating methionine codon into a valine codon thereby abolishing translation; (2) a thymine to cytosine transition at codon 370 changes a methionine to a threonine residue; (3) a cytosine to thymine transition at codon 367 changes a histidine to a tyrosine residue.
Sequence analysis of the tyrosinase coding region from an individual with tyrosinase-negative oculocutaneous albinism revealed that the patient was a compound heterozygote.
Among all biomarkers, urinary NGAL measured at day 3 had the greatest accuracy for differential diagnosis between ATN and other types of AKI (area under the receiver operating characteristic curve, 0.87; 95% confidence interval, 0.78-0.95).
In a systematic review and meta-analysis, we found that urine levels of IL18 and NGAL from patients with cirrhosis discriminate between those with ATN and other types of kidney impairments, with AUC values of 0.88 and 0.89, respectively.
New biomarkers of kidney injury, such as neutrophil gelatinase-associated lipocalin and interleukin-18, represent useful tools in refining the discrimination between HRS and ATN.
We performed a systematic review and meta-analysis of published studies to determine whether urine levels of interleukin (IL)18 and lipocalin 2 or neutrophil gelatinase-associated lipocalin (NGAL) are associated with the development of ATN in patients with cirrhosis.
These findings indicated that Bmi-1 played a critical role in the protection from ATN by maintaining mobilization of RSCs and would be a novel therapeutic target for preventing the progression of ATN.
Only urine NAG levels were significantly higher in patients with ATN than those with PRA or HRS (116.1 ± 46.8 U/g vs 39.4 ± 20.2 or 54.0 ± 19.2 U/g urinary creatinine, all P < 0.05).