TY - JOUR
T1 - Identification of a rare germline NBN gene mutation by whole exome sequencing in a lung-cancer survivor from a large family with various types of cancer
AU - Marafie, Makia J.
AU - Dashti, Mohammed
AU - Al-Mulla, Fahd
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Nijmegen breakage syndrome is an autosomal recessive disorder caused by biallelic mutation in NBN gene. It is characterized by microcephaly, growth retardation, immuno-deficiency and cancer predisposition. The monoallelic carriers of NBN gene are also reported to be at increased risk of developing various types of malignancy. We have investigated an individual with lung cancer from an extended family segregating different types of hereditary cancer over several generations, including lung, breast, ovarian, colon, prostate and renal cancers. By using next generation whole exome sequencing approach, we identified a rare heterozygous frameshift mutation in NBN gene; c.93_94delTG (Ala32HisfsTer4), which is predicted to be pathogenic together with 3 other variants; 2 being in the BRCA1 gene, c.1648A > C (p.Asn550His) and c.536A > G (p.Tyr179Cys), and one in RAD50 gene, c.3539G > A (p.Arg1180Gln). Some of the variants were also found in six out of eight clinically normal relatives, but in different combinations. To our knowledge, this is the first report of NBN gene mutation in an individual with lung cancer in the Arab world. Reporting such findings may aid in variants’ risk classification and clinical decision in the future.
AB - Nijmegen breakage syndrome is an autosomal recessive disorder caused by biallelic mutation in NBN gene. It is characterized by microcephaly, growth retardation, immuno-deficiency and cancer predisposition. The monoallelic carriers of NBN gene are also reported to be at increased risk of developing various types of malignancy. We have investigated an individual with lung cancer from an extended family segregating different types of hereditary cancer over several generations, including lung, breast, ovarian, colon, prostate and renal cancers. By using next generation whole exome sequencing approach, we identified a rare heterozygous frameshift mutation in NBN gene; c.93_94delTG (Ala32HisfsTer4), which is predicted to be pathogenic together with 3 other variants; 2 being in the BRCA1 gene, c.1648A > C (p.Asn550His) and c.536A > G (p.Tyr179Cys), and one in RAD50 gene, c.3539G > A (p.Arg1180Gln). Some of the variants were also found in six out of eight clinically normal relatives, but in different combinations. To our knowledge, this is the first report of NBN gene mutation in an individual with lung cancer in the Arab world. Reporting such findings may aid in variants’ risk classification and clinical decision in the future.
KW - Arab
KW - BRCA1
KW - Lung cancer
KW - NBN
KW - Next generation sequencing
KW - Whole-exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=84995489572&partnerID=8YFLogxK
U2 - 10.1007/s10689-016-9954-9
DO - 10.1007/s10689-016-9954-9
M3 - Article
C2 - 27844240
AN - SCOPUS:84995489572
VL - 16
SP - 389
EP - 394
JO - Familial Cancer
JF - Familial Cancer
SN - 1389-9600
IS - 3
ER -