Patients with NAXE-related mitochondrial encephalopathy exhibit developmental delay, cognitive regression, altered consciousness, abnormalities in eye movement (including nystagmus), muscle weakness, respiratory failure, seizure, ataxia, and gait disturbance at the age of 1 to 2 years. The disease is characterized by fluctuating symptoms over time, often exacerbated by febrile illness; it is progressive and fatal in the long term¹.

Prevalence

Single proband found in Japanese cohort¹.

Age of Onset

Single repeat expansion case had onset at 13 months, while NAXE-related mitochondrial encephalopathy more generally has predominately infantile onset, extending to 20y or older¹.

HPO Terms

–

Association

Mendelian

Locus

hg19 chr1:156561557-156561575

hg38 chr1:156591765-156591783

t2t chr1:155728131-155728159

Details

Benign range (2-7) alleles established by 484 control alleles and validated with orthogonal databases, while single proband had expansion of ~200 repeats inherited from mother via uniparental disomy¹. While the repeat expansion is newly reported, other variants in the NAXE gene have previously been associated with mitochondrial encephalopathy.

Mechanism

LoF

Reduced NAXE expression from expansion in promoter; hypermethylation was detected at and downstream of the repeat sequence in the proband as well as the maternal copy of the expanded allele, which was not present in the maternal normal range allele nor in the controls¹

Detection

Year

2024¹

Location in Gene

5' UTR

Gene Strand

Alleles

Ref. Motif

GGGCC

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

GGGCC

Pathogenic (gene)

CCGGG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

References

Direct supporting references for info on this page.

Biallelic GGGCC repeat expansion leading to NAXE-related mitochondrial encephalopathy.

Kokoro,Ozaki, Yukiko,Yatsuka, Yoshinobu,Oyazato, Atsushi,Nishiyama, Kazuhiro R,Nitta, Yoshihito,Kishita, Takuya,Fushimi, Masaru,Shimura, Shohei,Noma, Yohei,Sugiyama, Michihira,Tagami, Moe,Fukunaga, Hiroko,Kinoshita, Tomoko,Hirata, Wataru,Suda, Yasuhiro,Murakawa, Piero,Carninci, Akira,Ohtake, Kei,Murayama, Yasushi,Okazaki

NPJ genomic medicine · 2024-10-25

pmid:39455596

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

AIBP-LRP2-mediated HDL uptake restricts CXCR4

Lingping,Zhu, Minghong,Chen, Kechuan,Lin, Can,Du, Meilian,Yao, Jing,Chen, Jian,Zhang, Xunjie,Cheng, Dan,Wang, Yu,Liu, Lisha,Liu, Junyu,Chen, Yamei,Liu, Xin,Luo, Guogang,Zhang, Chuanchang,Li, Longhou,Fang, Yongping,Bai

Science advances · 2025-10-15

pmid:41091881

Locus NME NAXE

Disease

Locus

Alleles

References

Additional Literature