A homozygote variant in the tRNA splicing endonuclease subunit 54 causes pontocerebellar hypoplasia in a consanguineous Iranian family.

Molecular Genetics & Genomic Medicine
Afrooz SepahvandMasoud Garshasbi

Abstract

Homozygous loss-of-function mutations in TSEN54 (tRNA splicing endonuclease subunit 54; OMIM: 608755) cause different types of pontocerebellar hypoplasias (PCH) including PCH2, PCH4, and PCH5. The study aimed to determine the possible genetic factors contributing to PCH phenotypes in two affected male infants in an Iranian family. We subjected two affected individuals in a consanguineous Iranian family. To systematically investigate the susceptible gene(s), whole-exome sequencing was performed on the proband and a novel identified variant was confirmed by Sanger sequencing. We also analyzed 26 relatives in three generations using PCR-restriction fragment length polymorphism (PCR-RFLP) followed and confirmed by Sanger sequencing. Physical and medical examinations confirmed PCH in the patients. Besides, the proband showed bilateral moderate sensorineural hearing loss and structural heart defects as the novel phenotypes. The molecular findings also verified that two affected individuals were homozygote for the novel synonymous variant, NM_207346.2: c.1170G>A; p.(Val390Val), in TSEN54. PCR-RFLP and Sanger sequencing elucidated that the parents and 16 relatives were heterozygote for the novel variant. We identified a novel synonymou...Continue Reading

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Citations

Mar 31, 2021·Acta neurologica Belgica·Fardin SoleimanipourMasoud Garshasbi
Aug 11, 2021·Irish Journal of Medical Science·Mohammad Vafaee-ShahiMasoumeh Falah

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Methods Mentioned

BETA
protein folding
PCR
electrophoresis

Software Mentioned

Phenolyzer
SpliceAid2
BrainSpan
ScanProsite
RNAsnp
ConSurf
BLAST
KineFold
Face2Gene
mFold

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