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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

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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

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.

Figures

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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