Expanding the phenotypic spectrum associated with CFAP43 mutations: a case report
of familial male infertility with respiratory manifestations
#MMPMID41341611
Awad F
; Abukhaizaran R
; Al Jabi S
; Nabilsi M
; Ayasa LA
; AbuAlrob MA
; Owienah H
; Kassem H
; Kanaan M
Front Reprod Health
2025[]; 7
(?): 1609938
PMID41341611
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AIMS: Multiple morphological abnormalities of the sperm flagella (MMAF)
represents a rare and severe form of male infertility, characterized by defects
in sperm flagella. Mutations in genes essential for flagellar function, such as
CFAP43, have been implicated in MMAF. Flagella and motile cilia share a conserved
axonemal structure essential for their motile function and the
asthenospermia-related infertility of MMAF overlaps with primary ciliary
dyskinesia (PCD) symptoms, characterized by chronic airway disease and
infertility due to ciliary and flagellar dysfunction. This study investigates the
genetic basis of MMAF in two siblings, who also exhibited respiratory symptoms.
METHODS: Clinical assessment and semen analysis were conducted for two brothers
presenting with infertility and chronic respiratory symptoms. Whole-exome
sequencing (WES) was performed to identify potential genetic defects. RESULTS:
Both siblings exhibited classic MMAF features, including asthenospermia with
various flagellar abnormalities, in addition to chronic respiratory symptoms
including sinusitis and wet cough. WES identified a novel homozygous missense
genetic variation in CFAP43 [c.421T>A p.(Trp141Arg)]. CONCLUSION: Our findings
provide additional evidence of the genetic contribution of CFAP43 in MMAF and
suggest an expanded phenotypic spectrum of CFAP43-associated conditions to
encompass chronic respiratory symptoms attributed to airway ciliary dysfunction.
Further research is needed to uncover the underlying mechanisms linking CFAP43
mutations to these phenotypes.
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