PMID- 33840063
OWN - NLM
STAT- MEDLINE
DCOM- 20220407
LR  - 20221207
IS  - 1863-4362 (Electronic)
IS  - 0021-1265 (Linking)
VI  - 191
IP  - 2
DP  - 2022 Apr
TI  - Clinical and molecular features of two diabetes families carrying mitochondrial 
      ND1 T3394C mutation.
PG  - 749-758
LID - 10.1007/s11845-021-02620-4 [doi]
AB  - BACKGROUND: Mutations in mitochondrial DNA (mtDNA) are found to be associated 
      with type 2 diabetes mellitus (T2DM). However, the molecular pathogenesis of 
      these mutations in T2DM is still poorly understood. METHODS: In this study, we 
      report here the molecular features of two Han Chinese families with maternally 
      transmitted T2DM. The matrilineal relatives are undergoing clinical, biochemical, 
      genetic evaluations, and molecular analysis. Furthermore, the entire 
      mitochondrial genomes of these matrilineal relatives are screened by PCR-Sanger 
      sequencing. RESULTS: The age at onset of T2DM of these participants varies from 
      28 to 71 years, with an average of 43 years. Molecular analysis of mitochondrial 
      genomes identifies the existence of ND1 T3394C mutation in both families, 
      together with sets of variants belonging to mitochondrial haplogroup Y2 and M9a. 
      The m.T3394C mutation is localized at very conserved tyrosine at position 30 of 
      ND1, may result the failure in ND1 mRNA metabolism, and lead to mitochondrial 
      dysfunction. Moreover, sequence analysis of matrilineal relatives in Family 1 
      identifies the m.A14693G mutation which occurs in the TPsiC-loop of tRNA(Glu) 
      (position 54), and is critical to the structural formation and stabilization of 
      this tRNA. Thus, m.A14693G mutation may cause the impairment in tRNA metabolism, 
      thereby worsens the mitochondrial dysfunction caused by ND1 T3394C mutation. 
      However, no functional mtDNA variants are identified in Family 2 which suggest 
      that mitochondrial haplogroup may not play an important role in diabetes 
      expression. CONCLUSIONS: Our study indicates that mitochondrial ND1 T3394C 
      mutation is involved in the pathogenesis of maternally inherited T2DM in these 
      families.
CI  - (c) 2021. Royal Academy of Medicine in Ireland.
FAU - You, Xiaohong
AU  - You X
AD  - Department of Obstetrics and Gynecology, The Affiliated Traditional Chinese 
      Medicine Hospital of Southwest Medical University, Luzhou, 646000, China.
FAU - Huang, Xueming
AU  - Huang X
AD  - Department of Emergency, Luzhou Maternal and Child Health and Family Planning 
      Service Center, Luzhou, 646000, China.
FAU - Bi, Luowen
AU  - Bi L
AD  - Department of Obstetrics and Gynecology, The Affiliated Traditional Chinese 
      Medicine Hospital of Southwest Medical University, Luzhou, 646000, China.
FAU - Li, Rui
AU  - Li R
AD  - Department of Obstetrics and Gynecology, South Hospital of Fujian Provincial 
      Hospital, Fuzhou, 350007, China.
FAU - Zheng, Lin
AU  - Zheng L
AD  - Department of Obstetrics and Gynecology, South Hospital of Fujian Provincial 
      Hospital, Fuzhou, 350007, China.
FAU - Xin, Changzheng
AU  - Xin C
AD  - Department of Obstetrics and Gynecology, South Hospital of Fujian Provincial 
      Hospital, Fuzhou, 350007, China. xincz001@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20210411
PL  - Ireland
TA  - Ir J Med Sci
JT  - Irish journal of medical science
JID - 7806864
RN  - 0 (DNA, Mitochondrial)
RN  - EC 1.6.99.3 (NADH Dehydrogenase)
RN  - EC 7.1.1.2 (MT-ND1 protein, human)
SB  - IM
MH  - Asian People
MH  - DNA, Mitochondrial/genetics
MH  - *Diabetes Mellitus, Type 2/genetics
MH  - Humans
MH  - Mutation
MH  - NADH Dehydrogenase/*genetics
MH  - Pedigree
OTO - NOTNLM
OT  - Chinese families
OT  - M.A14693G
OT  - M.T3394C
OT  - MtDNA mutations
OT  - T2DM
EDAT- 2021/04/12 06:00
MHDA- 2022/04/08 06:00
CRDT- 2021/04/11 20:58
PHST- 2020/12/09 00:00 [received]
PHST- 2021/04/04 00:00 [accepted]
PHST- 2021/04/12 06:00 [pubmed]
PHST- 2022/04/08 06:00 [medline]
PHST- 2021/04/11 20:58 [entrez]
AID - 10.1007/s11845-021-02620-4 [pii]
AID - 10.1007/s11845-021-02620-4 [doi]
PST - ppublish
SO  - Ir J Med Sci. 2022 Apr;191(2):749-758. doi: 10.1007/s11845-021-02620-4. Epub 2021 
      Apr 11.