Contiguous gene deletion of chromosome 2p16.3-p21 as a cause of Lynch syndrome Journal Article


Authors: Salo-Mullen, E. E.; Lynn, P. B.; Wang, L.; Walsh, M.; Gopalan, A.; Shia, J.; Tran, C.; Man, F. Y.; McBride, S.; Schattner, M.; Zhang, L.; Weiser, M. R.; Stadler, Z. K.
Article Title: Contiguous gene deletion of chromosome 2p16.3-p21 as a cause of Lynch syndrome
Abstract: Lynch syndrome is an autosomal dominant condition caused by pathogenic mutations in the DNA mismatch repair (MMR) genes. Although commonly associated with clinical features such as intellectual disability and congenital anomalies, contiguous gene deletions may also result in cancer predisposition syndromes. We report on a 52-year-old male with Lynch syndrome caused by deletion of chromosome 2p16.3-p21. The patient had intellectual disability and presented with a prostatic adenocarcinoma with an incidentally identified synchronous sigmoid adenocarcinoma that exhibited deficient MMR with an absence of MSH2 and MSH6 protein expression. Family history was unrevealing. Physical exam revealed short stature, brachycephaly with a narrow forehead and short philtrum, brachydactyly of the hands, palmar transverse crease, broad and small feet with hyperpigmentation of the soles. The patient underwent total colectomy with ileorectal anastomosis for a pT3N1 sigmoid adenocarcinoma. Germline genetic testing of the MSH2, MSH6, and EPCAM genes revealed full gene deletions. SNP-array based DNA copy number analysis identified a deletion of 4.8 Mb at 2p16.3-p21. In addition to the three Lynch syndrome associated genes, the deleted chromosomal section encompassed genes including NRXN1, CRIPT, CALM2, FBXO11, LHCGR, MCFD2, TTC7A, EPAS1, PRKCE, and 15 others. Contiguous gene deletions have been described in other inherited cancer predisposition syndromes, such as Familial Adenomatous Polyposis. Our report and review of the literature suggests that contiguous gene deletion within the 2p16-p21 chromosomal region is a rare cause of Lynch syndrome, but presents with distinct phenotypic features, highlighting the need for recognition and awareness of this syndromic entity. © 2017, Springer Science+Business Media Dordrecht.
Keywords: colorectal cancer; prostate cancer; lynch syndrome; chromosomal deletion; 2p
Journal Title: Familial Cancer
Volume: 17
Issue: 1
ISSN: 1389-9600
Publisher: Springer  
Date Published: 2018-01-01
Start Page: 71
End Page: 77
Language: English
DOI: 10.1007/s10689-017-0006-x
PROVIDER: scopus
PMCID: PMC5708147
PUBMED: 28555354
DOI/URL:
Notes: Article -- Export Date: 2 April 2018 -- Source: Scopus
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MSK Authors
  1. Liying Zhang
    89 Zhang
  2. Zsofia Kinga Stadler
    152 Stadler
  3. Anuradha Gopalan
    275 Gopalan
  4. Jinru Shia
    465 Shia
  5. Martin R Weiser
    346 Weiser
  6. Lu Wang
    139 Wang
  7. Mark Schattner
    103 Schattner
  8. Sean Matthew McBride
    111 McBride
  9. Michael Francis Walsh
    49 Walsh
  10. Patricio Bernardo Lynn
    7 Lynn
  11. Christina Tran
    4 Tran
  12. Fung Ying Man
    1 Man