This report describes ciliary dyskinesia, primary, 9, with or without situs inversus (CILD9), which shows recessive inheritance. The human gene implicated in this disease is DNAI2 (dynein, axonemal, intermediate chain 2). There is a high-ortholog of DNAI2 in Drosophila, Dnai2, along with two moderately-scoring orthologs, CG10859 and CG1571. Several alleles of Dnai2 have been generated, including an amorphic allele, several RNAi targeting constructs, and P-element insertinon lines.
Human DNAI2 has not been introduced into flies.
In Dnai2 mutants, the Johnston's organs (chordotonal organs in antennae, used to sense sound and vibration) had virtually no electrical response to pure tone sound frequencies, whereas in controls, auditory neurons correctly transmitted and amplified vibrations received by the antenna. Johnston's organ cilia in Dnai2-null flies lack the outer dynein arms. Dnai2 is also expressed in the testis, as seen by Dnai2-Gal4 expression, and although null mutant sperm were motile, they performed worse in sperm competition assays.
Drosophila orthologs of several other genes required for assembly of dynein arms and implicated in ciliary dyskinesia in human have been found to affect auditory perception in flies (see FBhh0000436 and FBhh0000437).
[updated Dec. 2019 by FlyBase; FBrf0222196]
Primary ciliary dyskinesia is a disorder characterized by chronic respiratory tract infections, abnormally positioned internal organs, recurrent ear infections (especially in children) and infertility (especially in males). About 50 percent of people with primary ciliary dyskinesia have a mirror-image reversal of their internal organs (situs inversus). [from Genetics Home Reference, primary ciliary dyskinesia; 2016.11.21]
[CILIARY DYSKINESIA, PRIMARY, 9; CILD9](https://omim.org/entry/612444)
[DYNEIN, AXONEMAL, INTERMEDIATE CHAIN 2; DNAI2](https://omim.org/entry/605483)
Primary ciliary dyskinesia (FBhh0000435) is a ciliopathy characterized by defects in cilia, leading to respiratory tract and ear infections, as well as infertility. Situs inversus is an abnormality of early development, causing a mirror-image reversal of organs in the chest and abdomen. [from Genetics Home Reference, primary ciliary dyskinesia; 2019.05.10.]
There have been multiple reports (pubmed:18950741, pubmed:23261302) of individuals with neonatal and recurrent respiratory distress (sinusitis, otitis, rhinitis), with some also showing situs inversus and/or infertility. [From MIM:612444, 2019.05.10.]
Primary ciliary dyskinesia 9 is caused by homozygous mutation in the DNAI2 gene, one of several genes that are causitive for primary ciliary dyskinesia. [From MIM:612444, 2019.05.10.]
In human cilia, loss-of-function mutations in IC2 proteins such as DNAI2 prevent the assembly of the entire outer arm complex: mutant cilia lack outer arms and their constituent heavy chain proteins (Karak et al. 2015, FBrf0230280).
In Drosophila, Dnai2 encodes a WD-repeat, dynein intermediate chain (IC) subgroup 2 protein that is expressed in cilia of the chordotonal organs of the antenna and femur of adults, and the larval pentascolopidial organ (Karak et al. 2015, FBrf0230280). Drosophila have cilia in Type I sense organs (including chordotonal organs) and in sperm flagella (Boekhoff-Falk and Eberl 2014, pubmed:24719289).
One human gene to multiple Drosophila genes, only one ortholog high-scoring.
Only high-scoring ortholog, best score.
