ClinVar

In 2 brothers and their maternal uncle (family PCD-10) with X-linked primary ciliary dyskinesia-36 (CILD36; 300991), Paff et al. (2017) identified a hemizygous 7-bp deletion (c.357_363del, NM_001169154.1) in the PIH1D3 gene, predicted to result in a frameshift and premature termination (Val120LeufsTer6). The mutation, which was found by targeted exome sequencing and confirmed by Sanger sequencing, was not found in the dbSNP, 1000 Genomes Project, Exome Variant Server, or ExAC databases. Analysis of patient cells showed 2 abnormal transcripts: one that included the deletion in exon 6 and another that skipped exon 6. Each mutant transcript altered the reading frame to introduce premature termination in exon 6 and exon 8, respectively, yielding truncated proteins of 125 and 181 residues, respectively. The normal full-length protein is 214 residues. Only 1 of the transcripts appeared to be subject to nonsense-mediated mRNA decay. Western blot analysis of patient respiratory epithelial cells showed absence of the PIH1D3 protein, consistent with a loss of function.