The human dynein intermediate chain 2 gene (DNAI2): cloning, mapping, expression pattern, and evaluation as a candidate for primary ciliary dyskinesia

Abstract

Primary ciliary dyskinesia (PCD) is an autosomal recessive disease characterized by chronic sinusitis and bronchiectasis, and usually associated with hypofertility. Half of the patients present a situs inversus, defining the Kartagener's syndrome. This phenotype results from axonemal abnormalities of respiratory cilia and sperm flagella, i.e., mainly an absence of dynein arms. Recently, a candidate-gene approach, based on documented abnormalities of immotile strains of Chlamydomonas reinhardtii, allowed us to identify the first gene involved in PCD. Following the same strategy, we have characterized DNAI2, a human gene related to Chlamzydomonas IC69, and evaluated its possible involvement in a PCD population characterized by an absence of outer dynein arms. DNAI2, which is composed of 14 exons located at 17q25, is highly expressed in trachea and testis. No mutation was found in the DNAI2 coding sequence of the twelve patients investigated. However, ten intragenic polymorphic sites and an EcoRI RFLP have been identified, allowing the exclusion of DNAI2 in three consanguineous families.

Successful twin birth following blastocyst culture of embryos derived from the immotile ejaculated spermatozoa from a patient with primary ciliary dyskinesia: A case report

“…The first gene to be identified was DNAI1 and located on chromosome 9p13-21. It is highly expressed in the testes and trachea and contains 20 exons [47]. The second gene is the DNAH5 gene is located on chromosome 5p15-5p14 [48].…”

Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children

“…Realising the unlikelihood of knowing all cases, AFZELIUS [5] estimated the true prevalence for Sweden to be nearer to 1:10,000. In a long-term study on delayed atomic bomb effects carried out in Hiroshima and Nagasaki (both Japan), 16,566 persons underwent physical examination and chest radiography. In this very specific sample, four patients with PCD (aged 34-86 yrs) were detected, giving an estimate of 1:4,100 [6].…”

“…The majority of the genes identified (table 1) to date for autosomal recessive PCD variants (dynein, axonemal, intermediate chain 1 (DNAI1) and 2 (DNAI2) and heavy chain 5 (DNAH5) and 11 (DNAH11) and thioredoxin domain containing 3 (TXNDC3)) encode outer dynein arm (ODA) components [15][16][17][18][19][20], whereas only one gene (chromosome 14 open reading frame 104 (KTU)) is required for cytoplasmic preassembly of axonemal dyneins [21]. In addition mutations in the two genes, radial spoke head 9 homologue (RSPH9) and 4 homologue A (RSPH4A), have been reported in PCD patients with abnormalities of the central microtubular pair [22].…”

“…DNAI2 is the human orthologue of the Chlamydomonas intermediate ODA IC69 (also known as IC2) gene [16]. Mutations in this gene have been observed in three families with Kartagener's syndrome, PCD and ODA defects [15].…”

“…15) Negative ultrastructural analytical results using EM does not exclude a diagnosis of PCD, and, if there is a strong suspicion, further analyses should be carried out. 16) Patients in whom suspicion of PCD remains strong, and who have previously been screened for PCD using beat frequency assessment alone, should have their diagnosis reconsidered.…”