The silent mutation MLH1 c.543C>T resulting in aberrant splicing can cause Lynch syndrome: a case report.
The proband was a 67-year-old man with transverse and sigmoid colon cancer. Microsatellite instability analysis revealed a high frequency of microsatellite instability, and immunohistochemical staining showed the absence of both MLH1 and PMS2 proteins in the sigmoid colon cancer tissue specimens from the patient. DNA sequencing revealed a nucleotide substitution c.543C>T in MLH1, but this variant did not substitute an amino acid. The MLH1 c.543C>T variant was located 3 bases upstream from the end of exon 6 and created a new splice donor site 4 bases upstream from the end of exon 6. Consequently, the last 4 bases of exon 6 were deleted and frameshift occurred. Thus, the MLH1 c.543C>T silent mutation is considered 'pathogenic'.
Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital.|Hereditary Tumor Research Project, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
Tatsuro
T
Yamaguchi
Division of Molecular Diagnosis & Cancer Prevention, Saitama Cancer Center, Saitama, Japan.
Tomokazu
T
Wakatsuki
Division of Molecular Diagnosis & Cancer Prevention, Saitama Cancer Center, Saitama, Japan.
Mari
M
Kikuchi
Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
Shin-Ichiro
SI
Horiguchi
Division of Molecular Diagnosis & Cancer Prevention, Saitama Cancer Center, Saitama, Japan.
Kiwamu
K
Akagi
D000368:Aged; D017398:Alternative Splicing / Q000235:genetics; D001483:Base Sequence; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000235:genetics*; D010375:Pedigree; D017423:Sequence Analysis, RNA; D000069456:Silent Mutation / Q000235:genetics*
C501486:MLH1 protein, human; D000070957:MutL Protein Homolog 1
Lynch syndrome; colon cancer; silent mutation