Disease relevance of DNAH5

• Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry [1].
• Axonemal localization of the dynein component DNAH5 is not altered in secondary ciliary dyskinesia [2].
• Finally, this study demonstrates a link between ciliary function and situs determination, since compound mutation heterozygosity in DNAI1 results in PCD with situs solitus or situs inversus (KS) [3].
• PCD did not cause nerve degeneration or fibrous encapsulation when implanted immediately adjacent to the rat sciatic nerves [4].
• Impaired ciliary and flagellar functions resulting in male infertility and recurrent respiratory tract infections are found in patients suffering from primary ciliary dyskinesia (PCD) [5].

Psychiatry related information on DNAH5

• Two siblings had the clinical features of PCD and ciliary disorientation alone on repeated biopsies taken 10 yr apart [6].

High impact information on DNAH5

• We previously localized to chromosome 5p a PCD locus containing DNAH5, which encodes a protein highly similar to the Chlamydomonas gamma-dynein heavy chain [1].
• Primary ciliary dyskinesia (PCD, MIM 242650) is characterized by recurrent infections of the respiratory tract due to reduced mucociliary clearance and by sperm immobility [1].
• The histogram of neurite length of PC12 cells showed distinctive patterns on PCD that were absent on the controls [4].
• Furthermore, PCD promoted more vigorous neurite outgrowth in PC12 cells than tissue culture polystyrene, laminin, and poly(d-lysine) [4].
• The resultant biodegradable polymer, PCD, has pendent groups bearing dopamine functionalities [4].

Chemical compound and disease context of DNAH5

• Nitric oxide (NO) is measurable in nasal air of normal subjects and found to be low in cystic fibrosis (CF) and very low in PCD [7].
• Nasal and exhaled NO concentrations were compared before and after infusion of 500 mg x kg(-1) L-arginine, the substrate of NO synthases, in 11 cystic fibrosis (CF) patients, seven primary ciliary dyskinesia (PCD) syndrome patients, and 11 control subjects [8].
• The effect of peroral N-acetylcysteine (NAC) in patients with cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) was investigated [9].
• In order to evaluate the clinical value of the saccharin test as a practical and simple measure of mucociliary clearance, nasal mucociliary clearance (NMCC) and ciliary ultrastructure were studied in 22 patients suspected of having primary ciliary dyskinesia (PCD) based on the saccharin test [10].

Biological context of DNAH5

• CONCLUSIONS: DNAH5 is frequently mutated in patients with PCD exhibiting outer dynein arm defects and mutations cluster in five exons [11].
• METHODS: We screened 109 white PCD families originating from Europe and North America for presence of DNAH5 mutations by haplotype analyses and/or sequencing [11].
• This information is useful for establishing a clinical molecular genetic test for PCD [12].
• In 30 PCD families, we identified 33 novel (12 nonsense, 8 frameshift, 5 splicing, and 8 missense mutations) and two known DNAH5 mutations [11].
• In addition, we excluded linkage between this gene and similar PCD phenotypes in five other affected families, providing a clear demonstration of locus heterogeneity [13].

Anatomical context of DNAH5

• High-resolution immunofluorescence imaging of respiratory epithelial cells from eight patients with DNAH5 mutations showed mislocalization of mutant DNAH5 and accumulation at the microtubule organizing centers [11].
• Northern blot and in situ hybridization analyses revealed specific expression in testis, embryonic node, respiratory epithelium, and ependyma, resembling the DNAH5 expression pattern [14].
• RESULTS: In normal ciliated airway epithelium, DNAH5 and DNAH9 show a specific regional distribution along the ciliary axoneme, indicating the existence of at least two distinct ODA types [15].
• In contrast to respiratory cilia, sperm tails from a patient with DNAH5 mutations had normal ODA heavy chain distribution, suggesting different modes of ODA generation in these cell types [15].
• A subset of PC12 cells displayed high filopodium density on PCD [4].

Associations of DNAH5 with chemical compounds

• Because patients with PCD use cough clearance as an airway defense mechanism, we tested the hypothesis that aerosolized uridine-5'-triphosphate (UTP) would improve clearance during cough by its actions to stimulate Cl- secretion and mucin release by goblet cells [16].
• The ion-imprinted polymer based on HL1 proved to be particularly well adapted for yttrium extraction, having a sizeable capacity (8.9+/-0.2 mg g(-1) resin) and a fast rate of extraction (t(1/2)=1.7 min) [17].
• The amount of loosely-bound and acquired fluoride was determined after an experimental period of five days in plaque-covered, demineralized (PCD); clean, demineralized (CD); plaque-covered, sound (PCS); and clean sound enamel (CS) [18].
• The oxidation of metoprolol by human liver microsomes was impaired by histamine (IC50 values for ODM appearance at 25 microM: liver HL1 greater than 10, HL3 = 3.8 and HL4 = 3.7 mM) [19].
• Treatment of PMN with colchicine induced a red shift in the Laurdan excitation and emission spectra with the same trend observed in PMN from the PCD group [20].

Other interactions of DNAH5

• Disease-causing mutations have been reported in DNAI1 and DNAH5 encoding outer dynein arm (ODA) proteins of cilia [12].
• Applying a polymerase chain reaction-based approach, we identified a 1.5-kb partial complementary DNA of DNAH5 encoding a Chlamydomonas-related axonemal heavy dynein chain within the critical disease interval of this new PCD locus [21].
• Mislocalization of DNAH5 and DNAH9 in respiratory cells from patients with primary ciliary dyskinesia [15].

Analytical, diagnostic and therapeutic context of DNAH5

• Sequence analysis in individuals with PCD with randomization of LR asymmetry identified mutations resulting in non-functional DNAH5 proteins [1].
• Bronchial epithelial cells were obtained from normal donors and from a patient with primary ciliary dyskinesia (PCD) whose cilia demonstrated an absence of inner dynein arms by electron microscopy [22].
• We measured clearance during cough in 12 patients with PCD (ages 14 to 71 yr, FEV1 43% to 89% predicted) in a double blind, randomized, crossover study after aerosolization of a single dose of UTP (5 mg/ml, 3.5 ml) or vehicle (0.12% saline, 3.5 ml) [16].
• BACKGROUND: The airway cilia of patients with primary ciliary dyskinesia (PCD) exhibit several anomalies when studied by transmission electron microscopy, but little is known about the ultrastructural organisation of ciliary membranes in these patients [23].
• The chromosomal assignment of these dynein heavy chain genes which was confirmed by GeneBridge 4 radiation hybrid screening, will be extremely useful for linkage analysis efforts in patients with primary ciliary dyskinesia (PCD) [24].

References