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Pain correlates with germline mutation in schwannomatosis.

Abstract Schwannomatosis has been linked to germline mutations in the SMARCB1 and LZTR1 genes, and is frequently associated with pain.In a cohort study, we assessed the mutation status of 37 patients with clinically diagnosed schwannomatosis and compared to clinical data, whole body MRI (WBMRI), visual analog pain scale, and Short Form 36 (SF-36) bodily pain subscale.We identified a germline mutation in LZTR1 in 5 patients (13.5%) and SMARCB1 in 15 patients (40.5%), but found no germline mutation in 17 patients (45.9%). Peripheral schwannomas were detected in 3 LZTR1-mutant (60%) and 10 SMARCB1-mutant subjects (66.7%). Among those with peripheral tumors, the median tumor number was 4 in the LZTR1 group (median total body tumor volume 30 cc) and 10 in the SMARCB1 group (median volume 85cc), (P=.2915 for tumor number and P = .2289 for volume). mutation was associated with an increased prevalence of spinal schwannomas (100% vs 41%, P = .0197). The median pain score was 3.9/10 in the LZTR1 group and 0.5/10 in the SMARCB1 group (P = .0414), and SF-36 pain-associated quality of life was significantly worse in the LZTR1 group (P = .0106). Pain scores correlated with total body tumor volume (rho = 0.32471, P = .0499), but not with number of tumors (rho = 0.23065, P = .1696).We found no significant difference in quantitative tumor burden between mutational groups, but spinal schwannomas were more common in LZTR1-mutant patients. Pain was significantly higher in LZTR1-mutant than in SMARCB1-mutant patients, though spinal tumor location did not significantly correlate with pain. This suggests a possible genetic association with schwannomatosis-associated pain.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title medicine
Publication Year Start




PMID- 29384852
OWN - NLM
STAT- In-Process
LR  - 20180131
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Linking)
VI  - 97
IP  - 5
DP  - 2018 Feb
TI  - Pain correlates with germline mutation in schwannomatosis.
PG  - e9717
LID - 10.1097/MD.0000000000009717 [doi]
AB  - Schwannomatosis has been linked to germline mutations in the SMARCB1 and LZTR1
      genes, and is frequently associated with pain.In a cohort study, we assessed the 
      mutation status of 37 patients with clinically diagnosed schwannomatosis and
      compared to clinical data, whole body MRI (WBMRI), visual analog pain scale, and 
      Short Form 36 (SF-36) bodily pain subscale.We identified a germline mutation in
      LZTR1 in 5 patients (13.5%) and SMARCB1 in 15 patients (40.5%), but found no
      germline mutation in 17 patients (45.9%). Peripheral schwannomas were detected in
      3 LZTR1-mutant (60%) and 10 SMARCB1-mutant subjects (66.7%). Among those with
      peripheral tumors, the median tumor number was 4 in the LZTR1 group (median total
      body tumor volume 30 cc) and 10 in the SMARCB1 group (median volume 85cc),
      (P=.2915 for tumor number and P = .2289 for volume). mutation was associated with
      an increased prevalence of spinal schwannomas (100% vs 41%, P = .0197). The
      median pain score was 3.9/10 in the LZTR1 group and 0.5/10 in the SMARCB1 group
      (P = .0414), and SF-36 pain-associated quality of life was significantly worse in
      the LZTR1 group (P = .0106). Pain scores correlated with total body tumor volume 
      (rho = 0.32471, P = .0499), but not with number of tumors (rho = 0.23065, P =
      .1696).We found no significant difference in quantitative tumor burden between
      mutational groups, but spinal schwannomas were more common in LZTR1-mutant
      patients. Pain was significantly higher in LZTR1-mutant than in SMARCB1-mutant
      patients, though spinal tumor location did not significantly correlate with pain.
      This suggests a possible genetic association with schwannomatosis-associated
      pain.
FAU - Jordan, Justin T
AU  - Jordan JT
AD  - Department of Neurology.
AD  - Cancer Center, Massachusetts General Hospital, Boston, MA.
FAU - Smith, Miriam J
AU  - Smith MJ
AD  - Centre for Genomic Medicine, St Mary's Hospital, Division of Evolution and
      Genomic Sciences, School of Biological Sciences, University of Manchester,
      Manchester, UK.
FAU - Walker, James A
AU  - Walker JA
AD  - Department of Neurology.
AD  - Molecular Neurogenetics Unit, Center for Genomic Medicine.
FAU - Erdin, Serkan
AU  - Erdin S
AD  - Molecular Neurogenetics Unit, Center for Genomic Medicine.
FAU - Talkowski, Michael E
AU  - Talkowski ME
AD  - Department of Neurology.
AD  - Molecular Neurogenetics Unit, Center for Genomic Medicine.
FAU - Merker, Vanessa L
AU  - Merker VL
AD  - Department of Neurology.
FAU - Ramesh, Vijaya
AU  - Ramesh V
AD  - Department of Neurology.
AD  - Molecular Neurogenetics Unit, Center for Genomic Medicine.
FAU - Cai, Wenli
AU  - Cai W
AD  - Department of Radiology, Massachusetts General Hospital and Harvard Medical
      School.
FAU - Harris, Gordon J
AU  - Harris GJ
AD  - Department of Radiology, Massachusetts General Hospital and Harvard Medical
      School.
FAU - Bredella, Miriam A
AU  - Bredella MA
AD  - Department of Radiology, Massachusetts General Hospital and Harvard Medical
      School.
FAU - Seijo, Marlon
AU  - Seijo M
AD  - Cancer Center, Massachusetts General Hospital, Boston, MA.
FAU - Suuberg, Alessandra
AU  - Suuberg A
AD  - Molecular Neurogenetics Unit, Center for Genomic Medicine.
FAU - Gusella, James F
AU  - Gusella JF
AD  - Department of Neurology.
AD  - Molecular Neurogenetics Unit, Center for Genomic Medicine.
AD  - Department of Genetics, Harvard Medical School, Boston, MA.
FAU - Plotkin, Scott R
AU  - Plotkin SR
AD  - Department of Neurology.
AD  - Cancer Center, Massachusetts General Hospital, Boston, MA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
EDAT- 2018/02/01 06:00
MHDA- 2018/02/01 06:00
CRDT- 2018/02/01 06:00
PHST- 2018/02/01 06:00 [entrez]
PHST- 2018/02/01 06:00 [pubmed]
PHST- 2018/02/01 06:00 [medline]
AID - 10.1097/MD.0000000000009717 [doi]
AID - 00005792-201802020-00014 [pii]
PST - ppublish
SO  - Medicine (Baltimore). 2018 Feb;97(5):e9717. doi: 10.1097/MD.0000000000009717.