Mutations in SPATA5 Are Associated with Microcephaly, Intellectual Disability, Seizures, and Hearing Loss

  • Am J Hum Genet. 2015 Sep 3;97(3):457-64. doi: 10.1016/j.ajhg.2015.07.014.
Akemi J Tanaka  1 ,  Megan T Cho  2 ,  Francisca Millan  2 ,  Jane Juusola  2 ,  Kyle Retterer  2 ,  Charuta Joshi  3 ,  Dmitriy Niyazov  4 ,  Adolfo Garnica  5 ,  Edward Gratz  6 ,  Matthew Deardorff  7 ,  Alisha Wilkins  7 ,  Xilma Ortiz-Gonzalez  8 ,  Katherine Mathews  3 ,  Karin Panzer  9 ,  Eva Brilstra  10 ,  Koen L I van Gassen  10 ,  Catharina M L Volker-Touw  10 ,  Ellen van Binsbergen  10 ,  Nara Sobreira  11 ,  Ada Hamosh  11 ,  Dianalee McKnight  2 ,  Kristin G Monaghan  2 ,  Wendy K Chung  12
Affiliations
  • 1. Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA.
  • 2. GeneDx, Gaithersburg, MD 20877, USA.
  • 3. Departments of Pediatrics and Neurology, University of Iowa Children's Hospital, Iowa City, IA 52242, USA.
  • 4. Department of Pediatrics, Division of Medical Genetics, Ochsner Health System, New Orleans, LA 70121, USA.
  • 5. Arkansas Children's Hospital, Little Rock, AR 72202, USA.
  • 6. Child Neurology, Gratz & Shafrir, M.D., Baltimore, MD 21215, USA.
  • 7. Department of Pediatrics, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • 8. Departments of Pediatrics and Neurology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • 9. Department of Pediatrics, University of Iowa Children's Hospital, Iowa City, IA 52242, USA.
  • 10. Department of Medical Genetics, University Medical Center Utrecht, Utrecht 3584, the Netherlands.
  • 11. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
  • 12. Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: [email protected].
PMID: 26299366 DOI: 10.1016/j.ajhg.2015.07.014
Abstract

Using whole-exome Sequencing, we have identified in ten families 14 individuals with microcephaly, developmental delay, intellectual disability, hypotonia, spasticity, seizures, sensorineural hearing loss, cortical visual impairment, and rare autosomal-recessive predicted pathogenic variants in spermatogenesis-associated protein 5 (SPATA5). SPATA5 encodes a ubiquitously expressed member of the ATPase associated with diverse activities (AAA) protein family and is involved in mitochondrial morphogenesis during early spermatogenesis. It might also play a role in post-translational modification during cell differentiation in neuronal development. Mutations in SPATA5 might affect brain development and function, resulting in microcephaly, developmental delay, and intellectual disability.