Disease relevance of MCKD1

• Independent confirmation of the locations of MCKD1 and MCKD2 in other MCKD families, with or without hyperuricemia and gout, has been reported [1].
• BACKGROUND: Autosomal dominant medullary cystic kidney disease type 1 (MCKD1; Mendelian Inheritance in Man 174000) is a hereditary tubulointerstitial renal disease [2].
• The disease complex medullary cystic disease/familial juvenile hyperuricemic nephropathy (MCKD/FJHN) is characterized by alteration of urinary concentrating ability, frequent hyperuricemia, tubulo-interstitial fibrosis, cysts at the cortico-medullary junction and renal failure [3].
• While in NPH end-stage renal disease (ESRD) occurs in adolescence, ADMCKD leads to ESRD in adulthood [4].
• Macular corneal dystrophy (MCD; MIM 217800) is an autosomal recessive hereditary disease in which progressive punctate opacities in the cornea result in bilateral loss of vision, eventually necessitating corneal transplantation [5].

Psychiatry related information on MCKD1

• CONCLUSIONS: Once-daily doses of MCD and CON produced statistically significantly different PD effects on surrogate measures of behavior and performance among children with attention-deficit/hyperactivity disorder in the laboratory school setting [6].

High impact information on MCKD1

• The gene responsible for MCD type I has been mapped to chromosome 16q22, and that responsible for MCD type II may involve the same locus [5].
• MCD is classified into two subtypes, type I and type II, defined by the respective absence and presence of sulphated keratan sulphate in the patient serum, although both types have clinically indistinguishable phenotypes [5].
• In situ hybridization analysis did not detect CHST6 transcripts in corneal epithelium in an MCD type II patient, suggesting that the mutations found in type II lead to loss of cornea-specific expression of CHST6 [5].
• Such a preservation was observed in a group of membrane potential modulators including plant gamma-thionins, scorpion toxins, insect and scorpion defensins, bee venom apamin and MCD peptide, snake sarafotoxins, and human endothelins [7].
• MCD activity was increased more than fivefold, and the malonyl-CoA content was markedly diminished [8].

Chemical compound and disease context of MCKD1

• MCD is overwhelmingly the most frequent and most steroid-responsive of the three but commonly presents problems of massive edema, serious bacterial infections, and multiple relapses [9].
• Because of the prompt response of pediatric MCD to corticosteroids, steroid resistance in children has generally been defined as persistence of proteinuria after 1 month of daily followed by 1 month of intermittent prednisone administration [9].
• Nineteen patients with a previous myocardial infarction (17 men; mean left ventricular ejection fraction 44%+/-13%) underwent FDG MCD, FDG PET, resting echocardiography and technetium-99m tetrofosmin gated single-photon emission tomography (SPET) [10].

Biological context of MCKD1

• Our aim was to present and discuss the clinical, biochemical, sonographic and histopathological findings in six large Cypriot families in whom molecular analysis has confirmed linkage to the MCKD1 locus on chromosome 1q21 [11].
• METHODS: Haplotype analysis of a large Spanish family with MCKD was carried out to determinate genetic linkage to MCKD2 locus [12].
• In this consanguineous family there were three patients homozygous for the C255Y mutation, and multiple heterozygous cases, allowing the MCKD phenotypes associated with one or two mutant alleles to be compared [12].
• CONCLUSION: In all five families the association of MCKD2 with the disease was excluded by a multipoint LOD score <-2, thus suggesting the involvement of a third MCKD locus [13].
• Linkage analysis was used to study whether the Finnish families originating from a homogeneous population showed genetic linkage to the ADMCKD1 or ADMCKD2 loci [14].

Anatomical context of MCKD1

• MRI revealed a large MCD in the left parietal lobe with contiguous underlying periventricular heterotopia as well as a small contralateral PNH [15].
• Relative differences in neuronal density and size in FCD cases between the superficial (layer I and II) and deep cortical laminae (layer V and VI) were similar to that observed in other pathologies including mild MCD, temporal neocortex adjacent to hippocampal sclerosis as well as in a non-epilepsy surgical control group [16].
• The neuromuscular junction was intact in terms of normal jitter (expressed as MCD) and an absence of blocking [17].
• Erythrocyte protoporphyrin levels determined by magnetic circular dichroism correlated well with levels determined by the fluorimetric method of Piomelli, viz. a plot of MCD versus fluorimetry yielded a straight line relationship with a slope of 0.98 +/- 0.01, y-intercept of 0.05 +/- 0.35 and correlation coefficient of 0.99 [18].
• By immunohistochemistry, a focal or diffuse interstitial B cell infiltration could be detected in MGN patients (n = 63), which was absent or minimal in patients with MCD (n = 11) [19].

Associations of MCKD1 with chemical compounds

• In addition, the expression marker was able to predict steroid responsiveness in diagnostically challenging cases of MCD versus FSGS (n = 6) [20].
• Cyclosporine can also improve control in MCD, but continued treatment is often needed to maintain remission [9].
• Abs, CD, and MCD indicate that there are at least seven transitions below 35 000 cm(-1) which arise from tyrosinate ligand-to-metal-charge transfer (LMCT) transitions [21].
• The UV-vis spectrum of 1 shows a broad absorption band around 550 nm that is assigned to a charge-transfer transition from the hydroperoxo to a t(2g) d orbital of Fe(III) using resonance Raman and MCD spectroscopies and density functional (DFT) calculations [22].
• CD and MCD studies of the non-heme ferrous active site in (4-hydroxyphenyl)pyruvate dioxygenase: correlation between oxygen activation in the extradiol and alpha-KG-dependent dioxygenases [23].

Other interactions of MCKD1

• Homozygosity for uromodulin disorders: FJHN and MCKD-type 2 [12].
• Based on these findings it is unlikely that NPR1 is the same as the MCKD1 gene, although it is presently unknown whether it plays a disease modifying role [24].

Analytical, diagnostic and therapeutic context of MCKD1

• Immunohistochemistry on GCKD and MCKD/FJHN kidney biopsies revealed dense intracellular accumulation of uromodulin in tubular epithelia of the thick ascending limb of Henle's loop [3].
• Both focal neurological signs (p < 0.05) and focal electroencephalogram slowing (p < 0.05) independently correlated with MCD inactivity, confirming that fMRI showed neuronal functions of MCDs [25].
• The magnetic and electronic properties of a spin-frustrated ground state of an antiferromagnetically coupled 3-fold symmetric trinuclear copper complex (TrisOH) is investigated using a combination of variable-temperature variable-field magnetic circular dichroism (VTVH MCD) and powder/single-crystal EPR [26].
• Novel heme ligation in a c-type cytochrome involved in thiosulfate oxidation: EPR and MCD of SoxAX from Rhodovulum sulfidophilum [27].
• However, the variable-temperature MCD, resonance Raman, and redox properties (Em = -262 +/- 10 mV based on dye-mediated EPR redox titrations) are more characteristic of hydroxylase-type ferredoxins such as adrenodoxin [28].

References