High performing male with fragile X syndrome with an unmethylated FMR1 full mutation: The relevance of clinical and genetic correlations
Key Clinical Message A high performing male with an unmethylated full mutation in the fragile X messenger ribonucleoprotein 1 (FMR1) gene surpassed our expectations into young adulthood. Although initial genetic findings helped make a correct fragile X syndrome (FXS) determination, the report was in...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-06-01
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| Series: | Clinical Case Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ccr3.7371 |
| _version_ | 1797791707095367680 |
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| author | Meg Shieh Keren Amkraut Gail A. Spiridigliozzi Tatyana Adayev Kaylea Nicholson Allyn McConkie‐Rosell Marie McDonald Malinda Pennington Siby Sebastian Ave M. Lachiewicz |
| author_facet | Meg Shieh Keren Amkraut Gail A. Spiridigliozzi Tatyana Adayev Kaylea Nicholson Allyn McConkie‐Rosell Marie McDonald Malinda Pennington Siby Sebastian Ave M. Lachiewicz |
| author_sort | Meg Shieh |
| collection | DOAJ |
| description | Key Clinical Message A high performing male with an unmethylated full mutation in the fragile X messenger ribonucleoprotein 1 (FMR1) gene surpassed our expectations into young adulthood. Although initial genetic findings helped make a correct fragile X syndrome (FXS) determination, the report was insufficient. Ten years later, we repeated and conducted additional genetic and clinical studies to determine whether more information could assist with treatment and counseling. The genetic findings were very consistent with his high functioning and would have enabled us to be more confident about a good developmental outcome had they been available previously. As FXS enters the mainstream of well‐understood genetic disorders and technological advancements improve genetic tests, it should be clearer to clinical providers what a full FXS assessment could include to provide high quality information for care. For individuals with FXS who are high functioning, their families and clinical professionals would benefit from knowing more genetic findings, including, most importantly, methylation status, but also the FMR1 protein (FMRP) level and mRNA level. While we now know that obtaining only the CGG repeat number is not always adequate to inform accurate clinical care, future studies are likely to show the benefit of studying other biomarkers, such as mRNA levels. |
| first_indexed | 2024-03-13T02:22:34Z |
| format | Article |
| id | doaj.art-f999547a0f1f4565bd1cf48f5ab97266 |
| institution | Directory Open Access Journal |
| issn | 2050-0904 |
| language | English |
| last_indexed | 2024-03-13T02:22:34Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical Case Reports |
| spelling | doaj.art-f999547a0f1f4565bd1cf48f5ab972662023-06-30T07:34:08ZengWileyClinical Case Reports2050-09042023-06-01116n/an/a10.1002/ccr3.7371High performing male with fragile X syndrome with an unmethylated FMR1 full mutation: The relevance of clinical and genetic correlationsMeg Shieh0Keren Amkraut1Gail A. Spiridigliozzi2Tatyana Adayev3Kaylea Nicholson4Allyn McConkie‐Rosell5Marie McDonald6Malinda Pennington7Siby Sebastian8Ave M. Lachiewicz9Department of Chemistry Brown University Providence Rhode Island USADepartment of Pediatrics Duke University Health System Durham North Carolina USADepartment of Pediatrics Duke University Health System Durham North Carolina USADepartment of Human Genetics New York State Institute for Basic Research in Developmental Disabilities New York New York USADepartment of Communication Sciences Duke University Health Center Durham North Carolina USADepartment of Pediatrics Duke University Health System Durham North Carolina USADepartment of Pediatrics Duke University Health System Durham North Carolina USACollege of Education East Carolina University Greenville North Carolina USADepartment of Pathology Duke University Health System Durham North Carolina USADepartment of Pediatrics Duke University Health System Durham North Carolina USAKey Clinical Message A high performing male with an unmethylated full mutation in the fragile X messenger ribonucleoprotein 1 (FMR1) gene surpassed our expectations into young adulthood. Although initial genetic findings helped make a correct fragile X syndrome (FXS) determination, the report was insufficient. Ten years later, we repeated and conducted additional genetic and clinical studies to determine whether more information could assist with treatment and counseling. The genetic findings were very consistent with his high functioning and would have enabled us to be more confident about a good developmental outcome had they been available previously. As FXS enters the mainstream of well‐understood genetic disorders and technological advancements improve genetic tests, it should be clearer to clinical providers what a full FXS assessment could include to provide high quality information for care. For individuals with FXS who are high functioning, their families and clinical professionals would benefit from knowing more genetic findings, including, most importantly, methylation status, but also the FMR1 protein (FMRP) level and mRNA level. While we now know that obtaining only the CGG repeat number is not always adequate to inform accurate clinical care, future studies are likely to show the benefit of studying other biomarkers, such as mRNA levels.https://doi.org/10.1002/ccr3.7371fragile X syndromeunmethylated full mutationhigh functioningFMR1 |
| spellingShingle | Meg Shieh Keren Amkraut Gail A. Spiridigliozzi Tatyana Adayev Kaylea Nicholson Allyn McConkie‐Rosell Marie McDonald Malinda Pennington Siby Sebastian Ave M. Lachiewicz High performing male with fragile X syndrome with an unmethylated FMR1 full mutation: The relevance of clinical and genetic correlations Clinical Case Reports fragile X syndrome unmethylated full mutation high functioning FMR1 |
| title | High performing male with fragile X syndrome with an unmethylated FMR1 full mutation: The relevance of clinical and genetic correlations |
| title_full | High performing male with fragile X syndrome with an unmethylated FMR1 full mutation: The relevance of clinical and genetic correlations |
| title_fullStr | High performing male with fragile X syndrome with an unmethylated FMR1 full mutation: The relevance of clinical and genetic correlations |
| title_full_unstemmed | High performing male with fragile X syndrome with an unmethylated FMR1 full mutation: The relevance of clinical and genetic correlations |
| title_short | High performing male with fragile X syndrome with an unmethylated FMR1 full mutation: The relevance of clinical and genetic correlations |
| title_sort | high performing male with fragile x syndrome with an unmethylated fmr1 full mutation the relevance of clinical and genetic correlations |
| topic | fragile X syndrome unmethylated full mutation high functioning FMR1 |
| url | https://doi.org/10.1002/ccr3.7371 |
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