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. 2015 Sep 3;97(3):457-64.
doi: 10.1016/j.ajhg.2015.07.014. Epub 2015 Aug 20.

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

Free PMC article

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

Akemi J Tanaka et al. Am J Hum Genet. .
Free PMC article


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.


Figure 1
Figure 1
Variants in SPATA5 (A) Diagram of SPATA5 with variants identified in green. Missense and in-frame deletions are shown below, and gene-disrupting variants are shown above. (B) Sequence alignment of the CDC48 N-terminal domain (turquoise), AAA domains (yellow), and Walker A, Walker B, and second region of homology (SRH) motifs (blue text, underlined). A putative mitochondria-targeting sequence is highlighted in green, and potential ubiquitination sites are in gray. Residues altered in (A) are shown in bold red text. Species abbreviations are as follows: chimpanzee (Pantr, Pan troglodytes), fruit fly (Drome, Drosophila melanogaster), nematode (Cael, C. elegans), and budding yeast (Yeast, S. cerevisiae).

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