Familial Adenomatous Polyposis 4
In 2 sisters (family 1275) with autosomal recessive familial adenomatous polyposis-4 (FAP4; 617100), Adam et al. (2016) identified compound heterozygous mutations in the MSH3 gene: a 1-bp deletion (c.1148delA, NM_002439.4) in exon 7, resulting in a frameshift and premature termination (Lys383ArgfsTer32), and an A-to-C transversion in intron 21 (c.3001-2A-C; 600887.0002), resulting in aberrant splicing and premature termination (Val1001ArgfsTer16) that would alter the dimerization domain. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were filtered against the dbSNP, 1000 Genomes Project, Exome Variant Server, and ExAC databases, and an in-house database of 2,816 control exomes. The c.1148delA mutation was found at a low frequency (0.008%) in the ExAC database.
Endocrine Cancer, Somatic
In a primary endometrial cancer (608089) and in an endometrial carcinoma cell line, Risinger et al. (1996) found a somatic mutation in the MSH3 gene. The mutation resulted in a truncated product and consisted of a single nucleotide deletion, loss of an A/T basepair at position 1148. This change generated a premature nonsense codon and results in a protein 723 amino acids shorter than the wildtype gene product. No wildtype DNA sequence or gene product was evident in the cell line. Residual wildtype sequence in protein was present in the primary tumor sample, which may have resulted from contaminating normal cells. The mutation was absent in the DNA of normal cells from the patient.
