TY - JOUR
T1 - Mutation screening of fumarate hydratase by multiplex ligation-dependent probe amplification
T2 - detection of exonic deletion in a patient with leiomyomatosis and renal cell cancer
AU - Ahvenainen, Taru
AU - Lehtonen, Heli J
AU - Lehtonen, Rainer
AU - Vahteristo, Pia
AU - Aittomäki, Kristiina
AU - Baynam, Gareth
AU - Dommering, Charlotte
AU - Eng, Charis
AU - Gruber, Stephen B
AU - Grönberg, Henrik
AU - Harvima, Rauno
AU - Herva, Riitta
AU - Hietala, Marja
AU - Kujala, Minna
AU - Kääriäinen, Helena
AU - Sunde, Lone
AU - Vierimaa, Outi
AU - Pollard, Patrick J
AU - Tomlinson, Ian P M
AU - Björck, Erik
AU - Aaltonen, Lauri A
AU - Launonen, Virpi
N1 - (c) 2008 Elsevier Inc.
PY - 2008/6
Y1 - 2008/6
N2 - Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a syndrome predisposing to cutaneous and uterine leiomyomatosis as well as renal cell cancer and uterine leiomyosarcoma. Heterozygous germline mutations in the fumarate hydratase (FH, fumarase) gene are known to cause HLRCC. On occasion, no FH mutation is detected by direct sequencing, despite the evident HLRCC phenotype in a family. In the present study, to investigate whole gene or exonic deletions and amplifications in FH mutation-negative patients, we used multiplex ligation-dependent probe amplification technology. The study material comprised 7 FH mutation-negative HLRCC patients and 12 patients affected with HLRCC-associated phenotypes, including papillary RCC, early-onset RCC, uterine leiomyomas, or uterine leiomyosarcoma. A novel FH mutation, a deletion of FH exon 1 that encodes the mitochondrial signal peptide, was detected in one of the HLRCC patients (1/7). The patient with the FH mutation displayed numerous painful cutaneous leiomyomas and papillary type renal cell cancer. Our finding, together with the two patients with whole FH gene deletion who had been detected previously, suggests that exonic or whole-gene FH deletions are not a frequent cause of HLRCC syndrome.
AB - Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a syndrome predisposing to cutaneous and uterine leiomyomatosis as well as renal cell cancer and uterine leiomyosarcoma. Heterozygous germline mutations in the fumarate hydratase (FH, fumarase) gene are known to cause HLRCC. On occasion, no FH mutation is detected by direct sequencing, despite the evident HLRCC phenotype in a family. In the present study, to investigate whole gene or exonic deletions and amplifications in FH mutation-negative patients, we used multiplex ligation-dependent probe amplification technology. The study material comprised 7 FH mutation-negative HLRCC patients and 12 patients affected with HLRCC-associated phenotypes, including papillary RCC, early-onset RCC, uterine leiomyomas, or uterine leiomyosarcoma. A novel FH mutation, a deletion of FH exon 1 that encodes the mitochondrial signal peptide, was detected in one of the HLRCC patients (1/7). The patient with the FH mutation displayed numerous painful cutaneous leiomyomas and papillary type renal cell cancer. Our finding, together with the two patients with whole FH gene deletion who had been detected previously, suggests that exonic or whole-gene FH deletions are not a frequent cause of HLRCC syndrome.
KW - Base Sequence
KW - Carcinoma, Renal Cell
KW - DNA Primers
KW - Exons
KW - Fumarate Hydratase
KW - Humans
KW - Leiomyomatosis
KW - Ligase Chain Reaction
KW - Mutation
KW - Sequence Deletion
U2 - 10.1016/j.cancergencyto.2008.01.010
DO - 10.1016/j.cancergencyto.2008.01.010
M3 - Article
C2 - 18503824
SN - 1873-4456
VL - 183
SP - 83
EP - 88
JO - Cancer genetics and cytogenetics
JF - Cancer genetics and cytogenetics
IS - 2
ER -