BACKGROUND: Scoliosis is a feature of several @entity74 that are also associated with @entity449 , including @entity1614 , @entity17578 , and type-IV @entity4243 . Life-threatening complications of @entity449 can be decreased through early diagnosis. Genetic screening for mutations in populations at risk, such as @entity1 with @entity1615 , may improve recognition of these disorders. METHODS: The coding regions of five clinically actionable genes associated with @entity1635 ( @entity1414 , @entity6099 , @entity7382 , @entity2534 , and @entity7379 ) and @entity449 were sequenced in 343 @entity1615 cases. Gene variants that had minor allele frequencies of <0.0001 or were present in @entity1 disease mutation databases were identified. Variants were classified as pathogenic, likely pathogenic, or variants of unknown significance. RESULTS: Pathogenic or likely pathogenic mutations were identified in 0.9% (three) of 343 @entity1615 cases. Two @entity1 had pathogenic @entity7379 nonsense mutations consistent with type-III @entity17578 and one @entity1 had a pathogenic @entity6099 mutation with subsequent confirmation of @entity1614 . Variants of unknown significance in @entity1414 and @entity6099 were identified in 5.0% (seventeen) of 343 @entity1615 cases. Six @entity6099 variants were previously reported in @entity1 with @entity1614 , yet were considered variants of unknown significance based on the level of evidence. Variants of unknown significance occurred most frequently in @entity6099 and were associated with greater curve severity, systemic features of @entity1614 , and joint @entity8018 . CONCLUSIONS: Clinically actionable pathogenic mutations in genes associated with @entity1615 and @entity449 are rare in @entity1 with @entity1615 who are not suspected of having these disorders, although variants of unknown significance are relatively common. CLINICAL RELEVANCE: Routine genetic screening of all @entity1 with @entity1615 for mutations in clinically actionable @entity449 genes is not recommended on the basis of the high frequency of variants of unknown significance. Clinical evaluation and family history should heighten indications for genetic referral and testing.

Genetic Risk for @entity449 in XXXX .

@entity1 :: ('9606', 'Species') :: ['human', 'patients', 'patient'] @entity7382 :: ('7046', 'Gene') :: ['TGFBR1'] @entity1414 :: ('1281', 'Gene') :: ['COL3A1'] @entity449 :: ('MESH:D001014', 'Disease') :: ['aortic aneurysm disease', 'aortic aneurysm'] @entity1615 :: ('OMIM:181800', 'Disease') :: ['adolescent idiopathic scoliosis'] @entity2534 :: ('7048', 'Gene') :: ['TGFBR2'] @entity7379 :: ('4088', 'Gene') :: ['SMAD3'] @entity1614 :: ('MESH:D008382', 'Disease') :: ['Marfan syndrome'] @entity17578 :: ('MESH:D055947', 'Disease') :: ['Loeys-Dietz syndrome'] @entity6099 :: ('2200', 'Gene') :: ['FBN1'] @entity1635 :: ('MESH:D012600', 'Disease') :: ['scoliosis'] @entity4243 :: ('MESH:D004535', 'Disease') :: ['Ehlers-Danlos syndrome'] @entity74 :: ('MESH:D030342', 'Disease') :: ['genetic disorders'] @entity8018 :: ('MESH:C536196', 'Disease') :: ['hypermobility']
@entity1615 :: (OMIM:181800,Disease) :: ['Adolescent Idiopathic Scoliosis']
