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Blueprint Genetics Skeletal Dysplasias Core Panel

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Blueprint Genetics Skeletal Dysplasias Core Panel Skeletal Dysplasias Core Panel Test code: MA3501 Is a 113 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of a skeletal dysplasia. The genes on this panel are included in the Comprehensive Skeletal Dysplasias and Disorders Panel and in the Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders Panel. About Skeletal Dysplasias Core The Skeletal Dysplasias Core Panel is designed to detect mutations responsible for various skeletal dysplasias. Some of the resulting skeletal dysplasias are severe and potentially lethal (such as thanatophoric dysplasia, different types of achondrogenesis and osteogenesis imperfecta type II). Other non-lethal skeletal dysplasias result in disproportionate short stature. Achondroplasia is the most common cause of disproportionate short stature worldwide. It is characterized by rhizomelic shortening of the limbs, exaggerated lumbar lordosis, brachydactyly, and macrocephaly with frontal bossing and midface hypoplasia. Type II collagen defects (mutations in COL2A1 genes) have been identified in a spectrum of disorders ranging from perinatally lethal conditions to those with only mild arthropathy. As many different skeletal dysplasias have similar clinical and radiological findings, multigene panel testing allows for efficient diagnostic testing. Identification of causative mutation(s) establishes the inheritance mode in the family and enables genetic counselling. In addition, identifying the causative mutation(s) provides essential information for the doctor taking care of the patient. This panel provides excellent diffential diagnostic power for the major genes causing skeletal dysplasias. Availability 4 weeks Gene Set Description Genes in the Skeletal Dysplasias Core Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ACAN# Spondyloepimetaphyseal dysplasia, aggrecan type, AD/AR 20 56 Spondyloepiphyseal dysplasia, Kimberley type, Osteochondritis dissecans, short stature, and early-onset osteoarthritis ACP5 Spondyloenchondrodysplasia with immune dysregulation AR 12 26 ADAMTS10 Weill-Marchesani syndrome AR 8 14 ADAMTSL2*,# Geleophysic dysplasia 3 AR 8 28 AGPS Rhizomelic chondrodysplasia punctata type 3 AR 4 8 ALPL Odontohypophosphatasia, Hypophosphatasia perinatal AD/AR 78 291 lethal, infantile, juvenile and adult forms ANKH Calcium pyrophosphate deposition disease (familial AD 13 20 chondrocalcinosis type 2), Craniometaphyseal dysplasia autosomal dominant type ARSE* Chondrodysplasia punctata X-linked recessive, XL 22 46 brachytelephalangic type (CDPX1) https://blueprintgenetics.com/ B3GALT6 Spondyloepimetaphyseal dysplasia with joint laxity, AR 17 27 Ehlers-Danlos syndrome BMP1 Osteogenesis imperfecta AR 7 21 BMPR1B Acromesomelic dysplasia, Demirhan, Brachydactyly AD/AR 12 23 C/Symphalangism-like pheno, Brachydactyly type A2, Pulmonary arterial hypertension (PAH) CA2 Osteopetrosis, with renal tubular acidosis AR 9 31 CANT1 Desbuquois dysplasia AR 20 28 CDC6 Meier-Gorlin syndrome (Ear-patella-short stature AR 2 2 syndrome) CDKN1C Beckwith-Wiedemann syndrome, IMAGE syndrome AD 35 81 CDT1 Meier-Gorlin syndrome (Ear-patella-short stature AR 6 12 syndrome) CHST3 Spondyloepiphyseal dysplasia with congenital joint AR 18 37 dislocations (recessive Larsen syndrome) CLCN7 Osteopetrosis AD/AR 15 98 COL10A1 Metaphyseal chondrodysplasia, Schmid AD 21 53 COL11A1 Marshall syndrome, Fibrochondrogenesis, Stickler AD/AR 34 94 syndrome type 2 COL11A2 Weissenbacher-Zweymuller syndrome, Deafness, AD/AR 29 57 Otospondylomegaepiphyseal dysplasia, Fibrochondrogenesis, Stickler syndrome type 3 (non- ocular) COL1A1 Ehlers-Danlos syndrome, Caffey disease, Osteogenesis AD 352 962 imperfecta type 1, Osteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4 COL1A2 Ehlers-Danlos syndrome, cardiac valvular form, AD/AR 186 509 Osteogenesis imperfecta type 1, Osteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4 COL2A1 Avascular necrosis of femoral head, Rhegmatogenous AD 180 561 retinal detachment, Epiphyseal dysplasia, with myopia and deafness, Czech dysplasia, Achondrogenesis type 2, Platyspondylic dysplasia Torrance type, Hypochondrogenesis, Spondyloepiphyseal dysplasia congenital (SEDC), Spondyloepimetaphyseal dysplasia (SEMD) Strudwick type, Kniest dysplasia, Spondyloperipheral dysplasia, Mild SED with premature onset arthrosis, SED with metatarsal shortening, Stickler syndrome type 1 COL9A1 Stickler syndrome recessive type, Multiple epiphyseal AD/AR 9 6 dysplasia type 6 (EDM6) COL9A2 Stickler syndrome, Multiple epiphyseal dysplasia type 2 AD/AR 7 12 (EDM2) https://blueprintgenetics.com/ COL9A3 Multiple epihyseal dysplasia type 3 (EDM3), Stickler AD/AR 10 14 syndrome recessive type COMP Pseudoachondroplasia, Multiple ephiphyseal dysplasia AD 43 186 CRTAP Osteogenesis imperfecta type 2, Osteogenesis imperfecta AR 12 30 type 3, Osteogenesis imperfecta type 4 CSPP1 Jeune asphyxiating thoracic dystrophy, Joubert syndrome AR 32 27 CTSK Pycnodysostosis AR 35 58 CUL7 3-M syndrome, Yakut short stature syndrome AR 26 83 CYP27B1 Vitamin D-dependent rickets AR 23 73 DHCR24 Desmosterolosis AR 6 9 DLL3 Spondylocostal dysostosis AR 12 26 DVL1 Robinow syndrome AD 17 19 DYM Dyggve-Melchior-Clausen dysplasia, Smith-McCort AR 22 34 dysplasia DYNC2H1 Short -rib thoracic dysplasia with or without polydactyly AR/Digenic 148 205 type 1, Short -rib thoracic dysplasia with or without polydactyly type 3, Asphyxiating thoracic dysplasia (ATD; Jeune), SRPS type 2 (Majewski) EBP Chondrodysplasia punctata, Male EBP disorder with XL 43 90 neurologic defects (MEND) EIF2AK3 SED, Wolcott-Rallison type AR 9 80 ENPP1 Arterial calcification, Hypophosphatemic rickets AD/AR 22 72 ESCO2 SC phocomelia syndrome, Roberts syndrome AR 30 31 EVC Weyers acrofacial dysostosis, Ellis-van Creveld syndrome AD/AR 58 83 EVC2 Ellis-van Creveld syndrome, Weyers acrodental dysostosis AD/AR 78 75 FAM20C Hypophosphatemia, hyperphosphaturia, dental anomalies, AR 13 25 intracerebral calcifications and osteosclerosis (Raine syndrome) FGF23 Tumoral calcinosis, hyperphosphatemic, AD/AR 10 17 Hypophosphatemic rickets FGFR1 Pfeiffer syndrome, Trigonocephaly, Hypogonadotropic AD/Digenic/Multigenic 72 257 hypogonadism, Osteoglophonic Dwarfism - Craniostenosis, Hartsfield syndrome FGFR2 Apert syndrome, Pfeiffer syndrome, Jackson-Weiss AD 100 154 syndrome, Lacrimoauriculodentodigital syndrome, Beare- Stevenson cutis gyrata syndrome, Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis, Craniofacial-skeletal-dermatological dysplasia, Crouzon syndrome, Bent bone dysplasia https://blueprintgenetics.com/ FGFR3 Lacrimoauriculodentodigital syndrome, Muenke AD/AR 54 77 syndrome, Crouzon syndrome with acanthosis nigricans, Camptodactyly, tall stature, and hearing loss (CATSHL) syndrome, Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia type 1, Thanatophoric dysplasia type 2, SADDAN FKBP10 Bruck syndrome 1, Osteogenesis imperfecta, type XI AR 20 44 FLNA Frontometaphyseal dysplasia, Osteodysplasty Melnick- XL 133 257 Needles, Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defects FLNB Larsen syndrome (dominant), Atelosteogenesis type 1, AD/AR 43 121 Atelosteogenesis type 3, Spondylo-carpal-tarsal dyspasia GDF5 Multiple synostoses syndrome, Fibular hypoplasia and AD/AR 23 53 complex brachydactyly, Acromesomelic dysplasia, Hunter- Thompson, Symphalangism, proximal, Chondrodysplasia, Brachydactyly type A2, Brachydactyly type C, Grebe dysplasia GNPAT Rhizomelic chondrodysplasia punctata, rhizomelic AR 8 14 HSPG2 Schwartz-Jampel syndrome, Dyssegmental dysplasia AD/AR 16 60 Silverman-Handmaker type, Dyssegmental dysplasia Rolland-Desbuquis type IFT140 Short -rib thoracic dysplasia with or without polydactyly, AR 38 63 Asphyxiating thoracic dysplasia (ATD; Jeune) IFT172 Retinitis pigmentosa, Short -rib thoracic dysplasia with or AR 22 25 without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune) IFT80 Short -rib thoracic dysplasia with or without polydactyly, AR 11 11 Asphyxiating thoracic dysplasia (ATD; Jeune) IHH Acrocapitofemoral dysplasia, Brachydactyly, Syndactyly AD/AR 12 32 type Lueken INPPL1 Opsismodysplasia AR 16 32 KAT6B Ohdo syndrome, SBBYS variant, Genitopatellar syndrome AD 47 73 LBR Pelger-Huet anomaly, Reynolds syndrome, AD/AR 22 24 Greenberg/HEM skeletal dysplasia, Hydrops-ectopic calcification-moth-eaten skeletal dysplasia LIFR Stuve-Wiedemann dysplasia, Schwartz-Jampel type 2 AR 12 32 syndrome LMX1B Nail-patella syndrome AD 26 194 LRP5* Van Buchem disease, Osteoporosis-pseudoglioma AD/AR/Digenic 57 196 syndrome, Hyperostosis, endosteal, Osteosclerosis, Exudative vitreoretinopathy, Osteopetrosis late-onset form type 1, LRP5 primary osteoporosis https://blueprintgenetics.com/ LTBP2 Weill-Marchesani syndrome, Microspherophakia and/or AR 21 27 megalocornea, with ectopia lentis and with or without secondary glaucoma, Glaucoma, primary congenital MATN3 Spondyloepimetaphyseal dysplasia Matrilin type, Multiple AD/AR 8 25 epiphyseal dysplasia type 5 (EDM5) MMP9 Metaphyseal anadysplasia AR 1 7 MYO18B Klippel-Feil syndrome 4, autosomal recessive, with AR 2 4 myopathy and facial dysmorphism NEK1 Short -rib thoracic dysplasia with or without polydactyly, AR/Digenic 22 23 SRPS type 2 (Majewski) NPR2 Acromesomelic dysplasia type Maroteaux, Epiphyseal AD/AR 32 75 chondrodysplasia, Miura, Short stature with nonspecific
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