Abstract
Lynch syndrome (LS) is an autosomal dominant inherited disorder, characterized by
a predisposition to various cancers, mainly colorectal cancer (CRC). LS is caused
by germline mutations in DNA mismatch repair genes i.e. mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6), and post-meiotic segregation increased 2 (PMS2). In this study, we report a novel germline frameshift mutation in the MLH1 gene [NM_000249: exon1: c.99dup p.(Glu34ArgfsTer4)] in a 34-year-old male patient
with LS. This MLH1 alteration has never been reported in any database or any publications. The frameshift
mutation in MLH1 gene [NM_000249: exon1: c.99dup p.(Glu34ArgfsTer4)] was confirmed by Sanger sequencing
conducted on peripheral blood of the proband. Meanwhile, Sanger sequencing results
revealed the proband's uncle was the carrier. As multiple downstream germline frameshift
mutations of this variation are pathogenic, such as MLH1 M35fs, N38fs, and S44fs, it is predicted that MLH1 p.(Glu34ArgfsTer4) might be also pathogenic. Meanwhile, this MLH1 mutation p.(Glu34ArgfsTer4) is predicted to be disease-causing by the MutationTaster
software, as the duplication c.99dupA introduced a premature stop codon early in the
translation, resulting in a non-functional protein. This study may contribute to the
mutational spectrum of MLH1 leading to LS.
Keywords
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Article info
Publication history
Published online: March 18, 2023
Accepted:
March 16,
2023
Received in revised form:
January 8,
2023
Received:
April 22,
2022
Identification
Copyright
© 2023 Published by Elsevier Inc.
