Severe spinal cord hypoplasia due to a novel ATAD3A compound heterozygous deletion

• DOI: 10.1016/j.ymgmr.2022.100912
• Publication Date: 2022-08-24T23:37:25Z
• Authors: Tomohiro Ebihara; Taro Nagatomo; Yohei Sugiyama; Tomoko Tsuruoka; Yoshiteru Osone; Masaru Shimura; Makiko Tajika; Keiko Ichimoto; Yuki Naruke; Nana Akiyama; Sze Chern Lim; Yukiko Yatsuka; Kazuhiro R. Nitta; Yoshihito Kishita; Takuya Fushimi; Atsuko Okazaki; Akira Ohtake; Yasushi Okazaki; Kei Murayama
• Keywords: Compound heterozygosity

Biallelic deletions extending into the ATPase family AAA-domain containing protein 3A (ATAD3A) gene lead to infantile lethality with severe pontocerebellar hypoplasia (PCH). However, only 12 such cases have been reported worldwide date, and genotype-phenotype correlations are not well understood. We describe associated same novel biallelic of ATAD3A ATAD3B/3A regions in Japanese siblings spinal cord multiple malformations, including PCH, leading neonatal death. The is essential for normal interaction between mitochondria endoplasmic reticulum important mitochondrial biosynthesis. were evaluated using whole-genome sequencing genetic diagnosis disease. Spinal lesions compound heterozygous deletion reported. In addition, was 19 base pairs long, which short compared those previously. This introduced a frameshift, resulting premature termination codon, expected be null allele. pathological findings atrophic showed gliosis tissue destruction gray white matter. as new central nervous system phenotype gene. should considered disease PCH.