ORPHA: 201; DO: 0081003;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 20p11.23 | ?Cowden syndrome 7 | 616858 | Autosomal dominant | 3 | SEC23B | 610512 |
A number sign (#) is used with this entry because of evidence that Cowden syndrome-7 (CWS7) is caused by heterozygous mutation in the SEC23B gene (610512) on chromosome 20p11. One such family has been reported.
For a general phenotypic description and discussion of genetic heterogeneity of Cowden syndrome, see CWS1 (158350).
Yehia et al. (2015) studied a large 5-generation family segregating autosomal dominant Cowden syndrome. The proband was a 60-year-old woman who presented with follicular variant papillary thyroid cancer (FvPTC) that had been diagnosed at age 43, goiter, breast fibroadenoma and papilloma, typical breast ductal hyperplasia, fibrocystic breast disease, trichilemmoma, papillomatous papules of the mucosa, gastrointestinal polyps, and uterine fibroids. Her daughter was diagnosed with thyroid cancer at 21 years of age, and her son had benign thyroid disease at age 15 years. She also had a sister diagnosed with thyroid cancer at age 51 years, and that sister had a daughter diagnosed with endometrial cancer at age 35 years. The proband's deceased mother had breast cancer, as did a maternal aunt, who was diagnosed at age 44 years; and her maternal grandmother was diagnosed with thyroid cancer at age 50 years and breast cancer at age 79. In addition, a male cousin had skin cancer at age 53 years, and a niece of the maternal grandmother had thyroid cancer at age 60 years.
In the proband from a large 5-generation family segregating autosomal dominant Cowden syndrome, Yehia et al. (2015) performed whole-exome sequencing and identified a heterozygous missense mutation in the SEC23B gene (V594G; 610512.0007); no variants were found in known Cowden syndrome-associated genes. Sanger sequencing confirmed segregation of V594G with disease in the family, and the variant was not found in the dbSNP (build 137), 1000 Genomes Project, or NHLBI ESP6500 databases. Analysis of SEC23B in 96 patients with Cowden syndrome or a Cowden syndrome-like phenotype revealed 3 patients with mutations in SEC23B, including 2 unrelated women who were heterozygous for the same missense mutation (V164L; 610512.0008); however, that variant has been reclassified as a variant of unknown significance. Yehia et al. (2015) also found overrepresentation of unique SEC23B variants in sporadic cases of thyroid cancer.
Reclassified Variants
The Y131H variant reported by Yehia et al. (2015) has been reclassified as a variant of unknown significance; see 610512.0008.
Yehia, L., Niazi, F., Ni, Y., Ngeow, J., Sankunny, M., Liu, Z., Wei, W., Mester, J. L., Keri, R. A., Zhang, B., Eng, C. Germline heterozygous variants in SEC23B are associated with Cowden syndrome and enriched in apparently sporadic thyroid cancer. Am. J. Hum. Genet. 97: 661-676, 2015. [PubMed: 26522472] [Full Text: https://doi.org/10.1016/j.ajhg.2015.10.001]