A novel loss-of-function variant in PNLDC1 inducing oligo-astheno-teratozoospermia and male infertility

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Si-Yi Zhao1, Lan-Lan Meng2,3, Zhao-Li Du4

  • 1The First Clinical College of Guangzhou Medical University, Guangzhou 511436, China.

Asian Journal of Andrology
|March 24, 2023
PubMed

Insights

A novel PNLDC1 gene variant causes male infertility with oligo-astheno-teratozoospermia (OAT). This study identifies a homozygous loss-of-function variant in PNLDC1, leading to abnormal sperm morphology and acrosome loss in affected individuals.

Area of Science:

  • Genetics
  • Reproductive Biology
  • Molecular Biology

Background:

  • Male infertility affects a significant portion of the reproductive-aged population.
  • Abnormal sperm parameters, including count, motility, and morphology, are key indicators of male infertility.
  • Genetic factors play a crucial role in the etiology of male infertility, with numerous genes identified.

Purpose of the Study:

  • To investigate the genetic basis of male infertility presenting as oligo-astheno-teratozoospermia (OAT) in a Chinese Han family.
  • To identify the specific genetic variant responsible for the observed phenotype in the affected patient.

Main Methods:

  • Whole-exome sequencing and Sanger sequencing were employed to identify genetic variants.
  • Sperm morphology was assessed using Hematoxylin and eosin staining.
  • Acrosome integrity was evaluated via peanut agglutinin staining.
  • Sperm chromosome disomy rates were analyzed.

Main Results:

  • A homozygous loss-of-function (LOF) variant (c.142C>T, p.Gln48Ter) in the PNLDC1 gene was identified as the causative mutation.
  • The patient's spermatozoa exhibited abnormal head morphology (microcephaly, tapering, globozoospermia) and acrosome defects.
  • A significantly elevated rate of chromosome disomy was observed in the patient's spermatozoa compared to controls.

Conclusions:

  • Loss-of-function variants in the PNLDC1 gene are implicated in male infertility with OAT.
  • PNLDC1 plays a critical role in sperm development, acrosome formation, and chromosomal integrity.
  • This finding expands the spectrum of PNLDC1-associated male infertility phenotypes.

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