AK7 – Primary Ciliary Dyskinesia

Autosomal recessive variants in AK7, encoding adenylate kinase 7 expressed in ciliated epithelia, have been implicated in primary ciliary dyskinesia (PCD). In a cohort of 31 unrelated PCD patients, direct sequencing revealed a homozygous frameshift variant c.1171dup (p.Tyr391fs) segregating with disease in two consanguineous families, with affected individuals presenting chronic sinusitis, bronchiectasis and glue ear ([PMID:22801010]). The limited number of unrelated probands and modest segregation data support a Limited clinical validity classification.

Functional assessment of patient nasal epithelial cultures demonstrated markedly reduced AK7 expression, impaired ciliary beat frequency and ultrastructural axonemal defects consistent with PCD pathology ([PMID:22801010]). Notably, other AK7 mutations (e.g., p.Leu673Pro) lead to multiple morphological abnormalities of the sperm flagellum without respiratory involvement ([PMID:29365104]), suggesting tissue-specific consequences of AK7 deficiency. Overall, existing genetic and experimental findings support a Limited autosomal recessive association of AK7 with PCD; further case series and functional studies are needed.

Key Take-home: AK7 should be included in autosomal recessive PCD gene panels, but additional evidence is required to confirm its definitive role.

References

• American journal of rhinology & allergy • 2012 • New adenylate kinase 7 (AK7) mutation in primary ciliary dyskinesia. PMID:22801010
• Human Molecular Genetics • 2018 • Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia. PMID:29365104

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