is a clinical-stage biopharmaceutical company developing novel RNA-modulating drug candidates (designed to be eukaryotic ribosomal selective glycosides) that are formulated to treat rare and ultra-rare premature stop codon
The Fha inactivation probably resulted from changes within the homopolymeric G tract (site: 1078-1087) from 10 Gs to 11 Gs in fhaB, resulting in a downstream stop codon
that produces a truncated FhaB protein (11).
The deletion causes a frameshift mutation and a premature stop codon
(p.Asn574LysfsTer19; NM_001135243) of the treacle protein.
Since the duplication c.910dupG introduced a premature stop codon
early in the translation (at position 306), the dimerization domain with PMS2/MLH3/PMS1, as well as the interaction domain with hExoI, would be lost, leading to a non-functional protein (Figure 2a).
The forward primer with a Xbal cut site and a His-tag overhang (5'ATTATCT AGACACCACCACCACCACCATGATGATGATGA TAAGAGCGTGAG3") and reverse primer with a Aatll cut site and stop codon
overhang (5'GCGCGACG TCTTAGAAGTTATGCACATCCTG3') were designed in accordance with the cloning strategy and were used to amplify TPD gene from pET32a-TPD vector.
By changing an A to an I within a codon, its "readout" (translation to amino acid) within the ribosome can be altered, leading to missense mutations (substitution of one amino acid for another), nonsense mutations (substitution of an amino acid for a STOP codon
), or STOP suppressions (substitution of a STOP condon for a sense codon, leading to a product with some random C terminal tail).
As is seen in table 1, we found an undescribed homozygous mutation in exon 4 of the GAA gene (c.730C>T p.Q244*), creating a premature stop codon
and leading to a truncated protein or loss of protein production.
This substitution is a nonsense variant predicted to lead to the alteration of a cysteine into a premature stop codon
on position 1484 (LAMA2:p.Cys1484X).
Thenucleotidechangepredicted an amino acid substitution of tryptophan to a premature stop codon
at residue 155 (W155X).
Direct sequencing of all 11 exons of PRKAR1A of this patient identified a 88 A to G mutation, which changes the initiator ATG to a GTG codon, abolishes the translational start codon but does not introduce a premature stop codon
Interestingly, we found that the g.451A>G mutation was a synonymous mutation whereas g.462-463CC insertion caused a frameshift mutation which both changed the amino acids after 23rd codon and generated a premature stop codon
at position 56 (Figure 2C, Figure 3).