Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters











Database
Language
Publication year range
1.
Lung ; 196(2): 231-238, 2018 04.
Article in English | MEDLINE | ID: mdl-29368042

ABSTRACT

PURPOSE: Primary ciliary dyskinesia (PCD) is characterised by repeated upper and lower respiratory tract infections, neutrophilic airway inflammation and obstructive airway disease. Different ultrastructural ciliary defects may affect lung function decline to different degrees. Lung clearance index (LCI) is a marker of ventilation inhomogeneity that is raised in some but not all patients with PCD. We hypothesised that PCD patients with microtubular defects would have worse (higher) LCI than other PCD patients. METHODS: Spirometry and LCI were measured in 69 stable patients with PCD. Age at testing, age at diagnosis, ethnicity, ciliary ultrastructure, genetic screening result and any growth of Pseudomonas aeruginosa was recorded. RESULTS: Lung clearance index was more abnormal in PCD patients with microtubular defects (median 10.24) than those with dynein arm defects (median 8.3, p = 0.004) or normal ultrastructure (median 7.63, p = 0.0004). Age is correlated with LCI, with older patients having worse LCI values (p = 0.03, r = 0.3). CONCLUSION: This study shows that cilia microtubular defects are associated with worse LCI in PCD than dynein arm defects or normal ultrastructure. The patient's age at testing is also associated with a higher LCI. Patients at greater risk of obstructive lung disease should be considered for more aggressive management. Differences between patient groups may potentially open avenues for novel treatments.


Subject(s)
Cilia/ultrastructure , Ciliary Motility Disorders/complications , Lung Diseases/etiology , Lung/physiopathology , Lung/ultrastructure , Microtubules/ultrastructure , Mucociliary Clearance , Adolescent , Adult , Age Factors , Child , Child, Preschool , Ciliary Motility Disorders/genetics , Ciliary Motility Disorders/pathology , Ciliary Motility Disorders/physiopathology , Female , Forced Expiratory Volume , Humans , Infant , Infant, Newborn , Lung Diseases/pathology , Lung Diseases/physiopathology , Male , Maximal Midexpiratory Flow Rate , Microscopy, Electron, Transmission , Risk Factors , Spirometry , Young Adult
2.
Biochem Biophys Res Commun ; 439(3): 369-72, 2013 Sep 27.
Article in English | MEDLINE | ID: mdl-23998934

ABSTRACT

Hypomyelination and congenital cataract (HCC, OMIM #610532) is a rare autosomal recessive disorder due to FAM126A mutations characterized by congenital cataract, progressive neurologic impairment, and myelin deficiency in the central and peripheral nervous system. We have identified two novel mutations in three affected members of two unrelated families. Two sibs harbouring a microdeletion causing a premature stop in the protein showed the classical clinical and neuroradiologic HCC picture. The third patient carrying a missense mutation showed a relatively mild clinical picture without peripheral neuropathy. A residual amount of hyccin protein in primary fibroblasts was demonstrated by functional studies indicating that missense mutations are likely to have less detrimental effects if compared with splice-site mutations or deletions that cause the full-blown HCC phenotype, including peripheral nervous system involvement.


Subject(s)
Cataract/congenital , Cataract/genetics , Charcot-Marie-Tooth Disease/genetics , Intracellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Mutation , Amino Acid Sequence , Brain/metabolism , Brain/pathology , Cataract/pathology , Charcot-Marie-Tooth Disease/pathology , Child , Female , Humans , Infant , Intracellular Signaling Peptides and Proteins/chemistry , Membrane Proteins/chemistry , Molecular Sequence Data , Pedigree , Sequence Alignment
SELECTION OF CITATIONS
SEARCH DETAIL