Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Zhou 2022 J Hum Genet

From Bioblast
Publications in the MiPMap
Zhou X, Lou X, Zhou Y, Xie Y, Han X, Dong Q, Ying X, Laurentinah MR, Zhang L, Chen Z, Li D, Fang H, Lyu J, Yang Y, Wang Y (2022) Novel biallelic mutations in TMEM126B cause splicing defects and lead to Leigh-like syndrome with severe complex I deficiency.

Β» J Hum Genet 68:239-46. PMID: 36482121 Open Access

Zhou Xiyue,  Lou Xiaoting,  Zhou Yuwei,  Xie Yaojun,  Han Xinyu,  Dong Qiyu,  Ying Xiaojie, Laurentinah Mahlatsi Refiloe,  Zhang Luyi,  Chen Zhehui,  Li Dongxiao,  Fang Hezhi,  Lyu Jianxin,  Yang Yanling,  Wang Ya (2022) J Hum Genet

Abstract: Leigh syndrome (LS)/Leigh-like syndrome (LLS) is one of the most common mitochondrial disease subtypes, caused by mutations in either the nuclear or mitochondrial genomes. Here, we identified a novel intronic mutation (c.82-2 A > G) and a novel exonic insertion mutation (c.290dupT) in TMEM126B from a Chinese patient with clinical manifestations of LLS. In silico predictions, minigene splicing assays and patients' RNA analyses determined that the c.82-2 A > G mutation resulted in complete exon 2 skipping, and the c.290dupT mutation provoked partial and complete exon 3 skipping, leading to translational frameshifts and premature termination. Functional analysis revealed the impaired mitochondrial function in patient-derived lymphocytes due to severe complex I content and assembly defect. Altogether, this is the first report of LLS in a patient carrying mutations in TMEM126B. Our data uncovers the functional effect and the molecular mechanism of the pathogenic variants c.82-2 A > G and c.290dupT, which expands the gene mutation spectrum of LLS and clinical spectrum caused by TMEM126B mutations, and thus help to clinical diagnosis of TMEM126B mutation-related mitochondrial diseases.

β€’ Bioblast editor: Plangger M

Labels: MiParea: Respiration, nDNA;cell genetics, Patients 

Stress:Mitochondrial disease  Organism: Human  Tissue;cell: Lymphocyte  Preparation: Intact cells  Enzyme: Complex I 

Coupling state: LEAK, ROUTINE, ET 

HRR: Oxygraph-2k 

CN, 2022-12