PMID- 34811812
OWN - NLM
STAT- MEDLINE
DCOM- 20220321
LR  - 20220321
IS  - 1098-2825 (Electronic)
IS  - 0887-8013 (Print)
IS  - 0887-8013 (Linking)
VI  - 36
IP  - 1
DP  - 2022 Jan
TI  - Late onset of type 2 diabetes is associated with mitochondrial tRNA(Trp) A5514G 
      and tRNA(Ser(AGY)) C12237T mutations.
PG  - e24102
LID - 10.1002/jcla.24102 [doi]
LID - e24102
AB  - BACKGROUND: Mitochondrial dysfunctions caused by mitochondrial DNA (mtDNA) 
      pathogenic mutations play putative roles in type 2 diabetes mellitus (T2DM) 
      progression. But the underlying mechanism remains poorly understood. METHODS: A 
      large Chinese family with maternally inherited diabetes and deafness (MIDD) 
      underwent clinical, genetic, and molecular assessment. PCR and sequence analysis 
      are carried out to detect mtDNA variants in affected family members, in addition, 
      phylogenetic conservation analysis, haplogroup classification, and pathogenicity 
      scoring system are performed. Moreover, the GJB2, GJB3, GJB6, and TRMU genes 
      mutations are screened by PCR-Sanger sequencing. RESULTS: Six of 18 matrilineal 
      subjects manifested different clinical phenotypes of diabetes. The average age at 
      onset of diabetic patients is 52 years. Screening for the entire mitochondrial 
      genomes suggests the co-existence of two possibly pathogenic mutations: tRNA(Trp) 
      A5514G and tRNA(Ser(AGY)) C12237T, which belongs to East Asia haplogroup G2a. By 
      molecular level, m.A5514G mutation resides at acceptor stem of tRNA(Trp) 
      (position 3), which is critical for steady-state level of tRNA(Trp) . Conversely, 
      m.C12237T mutation occurs in the variable region of tRNA(Ser(AGY)) (position 31), 
      which creates a novel base-pairing (11A-31T). Thus, the mitochondrial 
      dysfunctions caused by tRNA(Trp) A5514G and tRNA(Ser(AGY)) C12237T mutations, may 
      be associated with T2DM in this pedigree. But we do not find any functional 
      mutations in those nuclear genes. CONCLUSION: Our findings suggest that m.A5514G 
      and m.C12337T mutations are associated with T2DM, screening for mt-tRNA mutations 
      is useful for molecular diagnosis and prevention of mitochondrial diabetes.
CI  - (c) 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley 
      Periodicals LLC.
FAU - Yang, Liuchun
AU  - Yang L
AD  - Central Laboratory, the Fourth School of Clinical Medicine, Zhejiang Chinese 
      Medical University, Hangzhou, China.
FAU - Guo, Qinxian
AU  - Guo Q
AD  - Central Laboratory, the Affiliated Hangzhou First People's Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Leng, Jianhang
AU  - Leng J
AD  - Central Laboratory, the Affiliated Hangzhou First People's Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Wang, Keyi
AU  - Wang K
AD  - Central Laboratory, the Fourth School of Clinical Medicine, Zhejiang Chinese 
      Medical University, Hangzhou, China.
AD  - Central Laboratory, the Affiliated Hangzhou First People's Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Ding, Yu
AU  - Ding Y
AUID- ORCID: 0000-0003-1246-2563
AD  - Central Laboratory, the Affiliated Hangzhou First People's Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
LA  - eng
GR  - LY18H160062/Zhejiang Natural Science Foundation/
GR  - 2021RC022/Health Commission of Zhejiang Province/
PT  - Journal Article
DEP - 20211122
PL  - United States
TA  - J Clin Lab Anal
JT  - Journal of clinical laboratory analysis
JID - 8801384
RN  - 0 (DNA, Mitochondrial)
RN  - 9014-25-9 (RNA, Transfer)
RN  - Noninsulin-dependent diabetes mellitus with deafness
SB  - IM
MH  - Adult
MH  - Animals
MH  - DNA, Mitochondrial/*genetics
MH  - Deafness/*genetics
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mitochondrial Diseases/*genetics
MH  - Mutation/*genetics
MH  - Pedigree
MH  - RNA, Transfer/*genetics
PMC - PMC8761459
OTO - NOTNLM
OT  - MIDD
OT  - m.A5514G
OT  - m.C12237T
OT  - mt-tRNA mutations
COIS- None.
EDAT- 2021/11/24 06:00
MHDA- 2022/03/22 06:00
PMCR- 2021/11/22
CRDT- 2021/11/23 06:49
PHST- 2021/10/19 00:00 [revised]
PHST- 2021/09/25 00:00 [received]
PHST- 2021/10/26 00:00 [accepted]
PHST- 2021/11/24 06:00 [pubmed]
PHST- 2022/03/22 06:00 [medline]
PHST- 2021/11/23 06:49 [entrez]
PHST- 2021/11/22 00:00 [pmc-release]
AID - JCLA24102 [pii]
AID - 10.1002/jcla.24102 [doi]
PST - ppublish
SO  - J Clin Lab Anal. 2022 Jan;36(1):e24102. doi: 10.1002/jcla.24102. Epub 2021 Nov 
      22.