Germline mutation in DOK7 associated with fetal akinesia deformation sequence.
BACKGROUND: Fetal akinesia deformation sequence syndrome (FADS) is a heterogeneous disorder characterised by fetal akinesia and developmental defects including, in some case, pterygia. Multiple pterygium syndromes (MPS) are traditionally divided into prenatally lethal and non-lethal (such as Escobar...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2009
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| _version_ | 1826269757687463936 |
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| author | Vogt, J Morgan, N Marton, T Maxwell, S Harrison, B Beeson, D Maher, E |
| author_facet | Vogt, J Morgan, N Marton, T Maxwell, S Harrison, B Beeson, D Maher, E |
| author_sort | Vogt, J |
| collection | OXFORD |
| description | BACKGROUND: Fetal akinesia deformation sequence syndrome (FADS) is a heterogeneous disorder characterised by fetal akinesia and developmental defects including, in some case, pterygia. Multiple pterygium syndromes (MPS) are traditionally divided into prenatally lethal and non-lethal (such as Escobar) types. Previously, we and others reported that homozygous mutations in the fetal acetylcholine receptor gamma subunit (CHRNG) can cause both lethal and non-lethal MPS, demonstrating that pterygia resulted from fetal akinesia, and that mutations in the acetylcholine receptor subunits CHRNA1, CHRND, and Rapsyn (RAPSN) can also result in a MPS/FADS phenotype. METHODS: We hypothesised that mutations in other acetylcholine receptor related genes may interfere with neurotransmission at the neuromuscular junction and so we analysed 14 cases of lethal MPS/FADS without CHRNG, CHRNA1, CHRNB1, CHRND, or RAPSN mutations for mutations in DOK7. RESULTS: A homozygous DOK7 splice site mutation, c.331+1G>T, was identified in a family with three children affected with lethal FADS. Previously DOK7 mutations have been reported to underlie a congenital myaesthenic syndrome with a characteristic "limb girdle" pattern of muscle weakness. CONCLUSION: This finding is consistent with the hypothesis that whereas incomplete loss of DOK7 function may cause congenital myasthenia, more severe loss of function can result in a lethal fetal akinesia phenotype. |
| first_indexed | 2024-03-06T21:30:07Z |
| format | Journal article |
| id | oxford-uuid:446ae4d8-c60e-40ec-a118-026e3346f9d7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:30:07Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:446ae4d8-c60e-40ec-a118-026e3346f9d72022-03-26T15:01:21ZGermline mutation in DOK7 associated with fetal akinesia deformation sequence.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:446ae4d8-c60e-40ec-a118-026e3346f9d7EnglishSymplectic Elements at Oxford2009Vogt, JMorgan, NMarton, TMaxwell, SHarrison, BBeeson, DMaher, EBACKGROUND: Fetal akinesia deformation sequence syndrome (FADS) is a heterogeneous disorder characterised by fetal akinesia and developmental defects including, in some case, pterygia. Multiple pterygium syndromes (MPS) are traditionally divided into prenatally lethal and non-lethal (such as Escobar) types. Previously, we and others reported that homozygous mutations in the fetal acetylcholine receptor gamma subunit (CHRNG) can cause both lethal and non-lethal MPS, demonstrating that pterygia resulted from fetal akinesia, and that mutations in the acetylcholine receptor subunits CHRNA1, CHRND, and Rapsyn (RAPSN) can also result in a MPS/FADS phenotype. METHODS: We hypothesised that mutations in other acetylcholine receptor related genes may interfere with neurotransmission at the neuromuscular junction and so we analysed 14 cases of lethal MPS/FADS without CHRNG, CHRNA1, CHRNB1, CHRND, or RAPSN mutations for mutations in DOK7. RESULTS: A homozygous DOK7 splice site mutation, c.331+1G>T, was identified in a family with three children affected with lethal FADS. Previously DOK7 mutations have been reported to underlie a congenital myaesthenic syndrome with a characteristic "limb girdle" pattern of muscle weakness. CONCLUSION: This finding is consistent with the hypothesis that whereas incomplete loss of DOK7 function may cause congenital myasthenia, more severe loss of function can result in a lethal fetal akinesia phenotype. |
| spellingShingle | Vogt, J Morgan, N Marton, T Maxwell, S Harrison, B Beeson, D Maher, E Germline mutation in DOK7 associated with fetal akinesia deformation sequence. |
| title | Germline mutation in DOK7 associated with fetal akinesia deformation sequence. |
| title_full | Germline mutation in DOK7 associated with fetal akinesia deformation sequence. |
| title_fullStr | Germline mutation in DOK7 associated with fetal akinesia deformation sequence. |
| title_full_unstemmed | Germline mutation in DOK7 associated with fetal akinesia deformation sequence. |
| title_short | Germline mutation in DOK7 associated with fetal akinesia deformation sequence. |
| title_sort | germline mutation in dok7 associated with fetal akinesia deformation sequence |
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