A contiguous microdeletion syndrome at Xp23.13 with non-obstructive azoospermia and congenital cataracts

J Assist Reprod Genet. 2020 Feb;37(2):471-475. doi: 10.1007/s10815-019-01685-6. Epub 2020 Jan 9.


Non-obstructive azoospermia accounts for 10-15% of male infertility, resulting in 60% of all cases of azoospermia and affecting about 1% of the male population. About 30% of these cases are due to Y chromosome microdeletions, chromosome abnormalities, or hormonal disorders. Pathogenic variants in genes on the sex chromosomes have key roles in spermatogenic failure. The co-occurrence of azoospermia and congenital cataracts ranges between 1 in 165,000 and 1 in 500,000. Our 28-year-old patient with normal intelligence and abnormally shaped teeth presented with both disorders. A microarray revealed a microdeletion at Xp23.13 with a whole NHS gene deletion as well as a contiguous deletion of two other genes [SCML1 and RAI2]. This observation represents the first report of non-obstructive azoospermia with congenital cataracts and a contiguous deletion of the SCML1 gene, a transcript of which is exclusively expressed in the testis. SCML1 is the putative culprit gene, which requires functional study or animal experiments. Our analysis of 60 known spermatogenesis failure-related genes by whole-exome sequencing revealed no other candidate. The Nance-Horan syndrome due to pathogenic variants in the NHS gene at Xp23.13 including whole gene deletion does not have azoospermia as a feature. Our report adds to the completeness of genetic counseling for an individual with azoospermia and congenital cataracts.

Keywords: Azoospermia; Congenital cataracts; Microdeletion; SCML1 gene; Spermatogenesis.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Azoospermia / genetics*
  • Azoospermia / pathology
  • Cataract / congenital*
  • Cataract / genetics*
  • Cataract / pathology
  • Chromosome Aberrations*
  • Chromosome Deletion
  • Chromosomes, Human, X / genetics
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / pathology
  • Humans
  • Male
  • Oligospermia / genetics
  • Oligospermia / pathology
  • Spermatogenesis / genetics
  • Testis / growth & development
  • Testis / pathology
  • Tooth Abnormalities / genetics*
  • Tooth Abnormalities / pathology

Supplementary concepts

  • Nance-Horan syndrome