title: Exome analysis of connective tissue dysplasia: death and rebirth of clinical genetics?
abstract: Exome results are reported for two patients with connective tissue dysplasia, one refining a clinical diagnosis of Ehlers-Danlos to Marfan syndrome, the other suggesting arthrogryposis derived from maternofetal Stickler syndrome. Patient 1 had mutations in transthyretin (TTR), fibrillin (FBN1), and a calcium channel (CACNA1A) gene suggesting diagnoses of transthyretin amyloidosis, Marfan syndrome, and familial hemiplegic migraines, respectively. Patient 2 presented with arthrogryposis that was correlated with his mother's habitus and arthritis once COL2A1 mutations suggestive of Stickler syndrome were defined. Although DNA results often defy prediction by the best of clinicians, these patients illustrate needs for ongoing clinical scholarship (e.g., to delineate guidelines for management of mutations like that for hyperekplexia in Patient 2) and for interpretation of polygenic change that is optimized by clinical genetic/syndromology experience (e.g., suggesting acetazolamide therapy for Patient 1 and explaining arthrogryposis in Patient 2).
authors.affiliation: Departments of Pediatrics, Obstetrics and Gynecology, Texas Tech University Health Science Centers, Amarillo and Lubbock (Pediatrics), KinderGenome Pediatric Genetics, Dallas, Texas.
authors.forename: Golder N
authors.initials: GN
authors.lastname: Wilson
mesh_terms: D000328:Adult; D001176:Arthrogryposis / Q000175:diagnosis / Q000235:genetics; D002648:Child; D003238:Connective Tissue / Q000378:metabolism* / Q000473:pathology*; D004535:Ehlers-Danlos Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D059472:Exome; D005260:Female; D056726:Genetic Association Studies; D005826:Genetics, Medical / Q000639:trends; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male
keywords: Ehlers-Danlos syndrome; Marfan syndrome; Stickler syndrome; amyloidosis; clinical genetics; collagen type II; connective tissue dysplasia; exome sequencing; familial hemiplegic migraines; fibrillin; hyperekplexia; transthyretin