LZTR1 molecular genetic overlap with clinical implications for Noonan syndrome and schwannomatosis
Abstract Background Noonan syndrome (NS) is a genetic disorder characterized by developmental delays, typical facial gestalt and cardiovascular defects. LZTR1 variants have been recently described in patients with NS and schwannomatosis, but the association, inheritance pattern and management strate...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | BMC Medical Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12920-022-01304-x |
| _version_ | 1811294623177375744 |
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| author | Kirsten M. Farncombe Emily Thain Carolina Barnett-Tapia Hamid Sadeghian Raymond H. Kim |
| author_facet | Kirsten M. Farncombe Emily Thain Carolina Barnett-Tapia Hamid Sadeghian Raymond H. Kim |
| author_sort | Kirsten M. Farncombe |
| collection | DOAJ |
| description | Abstract Background Noonan syndrome (NS) is a genetic disorder characterized by developmental delays, typical facial gestalt and cardiovascular defects. LZTR1 variants have been recently described in patients with NS and schwannomatosis, but the association, inheritance pattern and management strategy has not been fully elucidated. Here, we review the contribution of LZTR1 in NS and describe a patient with a novel, likely pathogenic variant in LZTR1. Case presentation A female patient was diagnosed with clinical NS at 8 months of age. She presented in adulthood when a brain and spine MRI identified plexiform neurofibromas; however, she did not meet the clinical criteria for Neurofibromatosis type 1. No pathogenic variants were identified through molecular genetic analysis of NF1, SPRED1 and a multigene NS panel. Whole exome sequencing at age 23 identified a novel de novo likely pathogenic heterozygous variant in the LZTR1 gene denoted as c.743G>A (p.Gly248Glu). Serial MRIs have shown stable imaging findings and the patient is being followed clinically by cardiology, neurology and medical genetics. Conclusions We identified a novel mutation in the LZTR1 gene, not previously reported in association with NS. This report provides additional evidence to support for the assessment of schwannomatosis in patients with LZTR1-NS and may have overlap with Neurofibromatosis type 1. |
| first_indexed | 2024-04-13T05:20:11Z |
| format | Article |
| id | doaj.art-62ba543625d740ea856458c99669f680 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-04-13T05:20:11Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-62ba543625d740ea856458c99669f6802022-12-22T03:00:46ZengBMCBMC Medical Genomics1755-87942022-07-0115111510.1186/s12920-022-01304-xLZTR1 molecular genetic overlap with clinical implications for Noonan syndrome and schwannomatosisKirsten M. Farncombe0Emily Thain1Carolina Barnett-Tapia2Hamid Sadeghian3Raymond H. Kim4Toronto General Hospital Research Institute, University Health NetworkBhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, University Health NetworkDivision of Neurology, Department of Medicine, University Health Network, University of TorontoDivision of Neurology, Department of Medicine, University Health Network, University of TorontoDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Sinai Health SystemAbstract Background Noonan syndrome (NS) is a genetic disorder characterized by developmental delays, typical facial gestalt and cardiovascular defects. LZTR1 variants have been recently described in patients with NS and schwannomatosis, but the association, inheritance pattern and management strategy has not been fully elucidated. Here, we review the contribution of LZTR1 in NS and describe a patient with a novel, likely pathogenic variant in LZTR1. Case presentation A female patient was diagnosed with clinical NS at 8 months of age. She presented in adulthood when a brain and spine MRI identified plexiform neurofibromas; however, she did not meet the clinical criteria for Neurofibromatosis type 1. No pathogenic variants were identified through molecular genetic analysis of NF1, SPRED1 and a multigene NS panel. Whole exome sequencing at age 23 identified a novel de novo likely pathogenic heterozygous variant in the LZTR1 gene denoted as c.743G>A (p.Gly248Glu). Serial MRIs have shown stable imaging findings and the patient is being followed clinically by cardiology, neurology and medical genetics. Conclusions We identified a novel mutation in the LZTR1 gene, not previously reported in association with NS. This report provides additional evidence to support for the assessment of schwannomatosis in patients with LZTR1-NS and may have overlap with Neurofibromatosis type 1.https://doi.org/10.1186/s12920-022-01304-xNoonan syndromeNeurofibromasWhole exome sequencingLZTR1 |
| spellingShingle | Kirsten M. Farncombe Emily Thain Carolina Barnett-Tapia Hamid Sadeghian Raymond H. Kim LZTR1 molecular genetic overlap with clinical implications for Noonan syndrome and schwannomatosis BMC Medical Genomics Noonan syndrome Neurofibromas Whole exome sequencing LZTR1 |
| title | LZTR1 molecular genetic overlap with clinical implications for Noonan syndrome and schwannomatosis |
| title_full | LZTR1 molecular genetic overlap with clinical implications for Noonan syndrome and schwannomatosis |
| title_fullStr | LZTR1 molecular genetic overlap with clinical implications for Noonan syndrome and schwannomatosis |
| title_full_unstemmed | LZTR1 molecular genetic overlap with clinical implications for Noonan syndrome and schwannomatosis |
| title_short | LZTR1 molecular genetic overlap with clinical implications for Noonan syndrome and schwannomatosis |
| title_sort | lztr1 molecular genetic overlap with clinical implications for noonan syndrome and schwannomatosis |
| topic | Noonan syndrome Neurofibromas Whole exome sequencing LZTR1 |
| url | https://doi.org/10.1186/s12920-022-01304-x |
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