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Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Genetics: caused by heterozygous mutations in the gene ROR2; this encodes a receptorlike tyrosine kinase essential for normal chondrocyte growth and differentiation. ROR2 BDB-associated mutations typically cause truncation of either the N-terminal or C-terminal receptor of the intracellular tyrosine kinase domain. Homozygous mutations in the same gene cause the autosomal recessive form of Robinow syndrome.
Molecular Genetics of Cleidocranial Dysplasia
Published in Fetal and Pediatric Pathology, 2021
Jamshid Motaei, Arash Salmaninejad, Ebrahim Jamali, Imaneh Khorsand, Mohammad Ahmadvand, Sasan Shabani, Farshid Karimi, Mohammad Sadegh Nazari, Golsa Ketabchi, Fatemeh Naqipour
Most ST are isolated cases, but some may be hereditary and associated with some syndromes. In a review article, Lubinsky et al, reports about 8 genetic syndromes with strong evidence for ST [52]. Syndromes that show supernumerary teeth include cleidocranial dysplasia, familial adenomatous polyposis, trichorhinophalangeal syndrome type I, Rubinstein–Taybi syndrome, Nance–Horan syndrome, Opitz BBB/G syndrome, oculofaciocardiodental syndrome and autosomal dominant Robinow syndrome. Several members of a single kindred in the Kreiborg–Pakistani syndrome (OMIM 614188) and insulin resistant diabetes mellitus with acanthosis nigricans (OMIM 610549) have been reported with ST [52,55,56]. Some Mendelian disorder have ST: Fabry disease, Ellis–van Creveld syndrome, Apert and Crouzon syndromes, Hallermann–Streiff syndrome, Zimmermann–Laband syndrome and Ehlers–Danlos syndrome [52].
Clinical genomics and contextualizing genome variation in the diagnostic laboratory
Published in Expert Review of Molecular Diagnostics, 2020
James R. Lupski, Pengfei Liu, Pawel Stankiewicz, Claudia M. B. Carvalho, Jennifer E. Posey
Examining the patient’s personal genome in a family trio (proband + parents) exome sequencing (ES) manner, with computational filtering of rare variants inherited from one parent or the other, can enable the identification of the new mutation(s), and potential pathological variation contributing to the sporadic disease process as compared with inherited variant alleles [16,17]. The disease-associated new mutation can be: i) an entire chromosome as in nondisjunction trisomy 21 causing Down syndrome, ii) SV/CNV perturbing a gene’s dosage or expression or structure of a gene, perhaps APP gene dosage associated with early-onset dementia and an oncogene causing leukemia both as endophenotypes of Down syndrome, or iii) a W-C bp change, SNV, resulting in a pathogenic rare variant allele such as, for example, a DVL1 or DVL3 gene −1 frameshift allele causing autosomal dominant Robinow syndrome [18].
The biochemistry, signalling and disease relevance of RYK and other WNT-binding receptor tyrosine kinases
Published in Growth Factors, 2018
James P. Roy, Michael M. Halford, Steven A. Stacker
The skeletal and craniofacial defects of the Ryk knockout mice indicate the potential for involvement of RYK dysfunction in human disorders of the skeletal system. Given the known genetic involvement of WNT5A in Robinow syndrome (Person et al., 2010; Roifman et al., 2015) and the phenotypic similarities of Wnt5A−/− and Ryk−/−; Vangl2−/− mice, it was suggested that RYK may play a role in this rare musculoskeletal syndrome (Andre et al., 2012; Andre & Yang, 2013; Mazzeu, 2013). Another pathology characterized by abnormalities of the phalanges, Brachydactyly Type B, is also caused by ROR2 mutations (Oldridge et al., 2000; Schwabe et al., 2000). A mutation in RYK, seemingly reducing the receptor’s activity, has been found in a patient with cleft lip and palate (Watanabe et al., 2006). Further strengthening the link between aberrant signalling by WNT-binding RTKs and skeletal system abnormalities, PTK7 has been implicated in scoliosis, a disorder resulting in abnormal curvature of the spine. Ptk7 mutant zebrafish display scoliosis (Grimes et al., 2016; Hayes et al., 2014) and a missense mutation in the sixth Ig-like domain of PTK7, resulting in a loss of WNT/PTK7 signalling, was discovered in a scoliosis patient (Hayes et al., 2014).