New adenylate kinase 7 (AK7) mutation in primary ciliary dyskinesia.
BACKGROUND
Primary ciliary dyskinesia (PCD) is a congenital hereditary disease affecting 1/20,000-60,000 people that causes chronic sinusitis, bronchiectasis, sinus hypoplasia, secretory otitis media, and low fertility. The complexity and heterogeneity of the disease  make diagnosis difficult. Although the genetic origin of PCD is clear, mutations in only five genes have been associated with the disease, and, to date, no disease-causing gene has been identified. Recently, low levels of AK7 gene expression have been linked to PCD. This study was designed  to determine the mutational status of the AK7 gene in 31 PCD (17 PCD and 14 Kartagener syndrome diagnosed) patients compared with 40 healthy volunteers. We also determined the AK7 sequence in two families with members with PCD and investigated ciliary activity and ciliogenesis in one patient  with a mutation in AK7.


METHODS
We analyzed nasal mucociliary transport and cilial ultrastructure by electron microscopy and studied nasal ciliary beat frequency and beat pattern using high-resolution digital high speed video (DHSV) imaging. Mutation analyses were performed  by direct resequencing of the 18 exons of the AK7 gene. Air-liquid interface differentiated cultures were studied using DHSV imaging and histochemistry. AK7 gene expression was studied by real-time reverse-transcription polymerase chain reaction.


RESULTS
We identified  two mutations in the AK7 gene, the described single nucleotide polymorphism (rs2369679), and a new mutation (c.1214insT) that, to the best of our knowledge, has not been described previously. Family and functional studies indicated that c.1214insT could be related to PCD.


CONCLUSIONS
Our results indicate that AK7 may be involved in the development of PCD.
Research Foundation Of the University General Hospital of Valencia, Spain. mata_manroi@gva.es
Manuel
M
Mata
Javier
J
Lluch-Estellés
Miguel
M
Armengot
Irene
I
Sarrión
Carmen
C
Carda
Julio
J
Cortijo
D000263:Adenylate Kinase / Q000235:genetics* / Q000502:physiology; D000328:Adult; D002648:Child; D006801:Humans; D007619:Kartagener Syndrome / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction
C556108:AK7 protein, human; D000263:Adenylate Kinase