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Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7‐year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution
Author(s) -
Jackson Gail C.,
MittazCrettol Laureane,
Taylor Jacqueline A.,
Mortier Geert R.,
Spranger Juergen,
Zabel Bernhard,
Le Merrer Martine,
CormierDaire Valerie,
Hall Christine M.,
Offiah Amaka,
Wright Michael J.,
Savarirayan Ravi,
Nishimura Gen,
Ramsden Simon C.,
Elles Rob,
Bonafe Luisa,
SupertiFurga Andrea,
Unger Sheila,
Zankl Andreas,
Briggs Michael D.
Publication year - 2012
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21611
Subject(s) - cartilage oligomeric matrix protein , genetics , osteochondrodysplasia , achondroplasia , mutation , biology , dysplasia , gene , bioinformatics , pathology , medicine , osteoarthritis , anatomy , alternative medicine
Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are relatively common skeletal dysplasias resulting in short‐limbed dwarfism, joint pain, and stiffness. PSACH and the largest proportion of autosomal dominant MED (AD‐MED) results from mutations in cartilage oligomeric matrix protein ( COMP ); however, AD‐MED is genetically heterogenous and can also result from mutations in matrilin‐3 ( MATN3 ) and type IX collagen ( COL9A1 , COL9A2 , and COL9A3 ). In contrast, autosomal recessive MED (rMED) appears to result exclusively from mutations in sulphate transporter solute carrier family 26 ( SLC26A2 ). The diagnosis of PSACH and MED can be difficult for the nonexpert due to various complications and similarities with other related diseases and often mutation analysis is requested to either confirm or exclude the diagnosis. Since 2003, the European Skeletal Dysplasia Network (ESDN) has used an on‐line review system to efficiently diagnose cases referred to the network prior to mutation analysis. In this study, we present the molecular findings in 130 patients referred to ESDN, which includes the identification of novel and recurrent mutations in over 100 patients. Furthermore, this study provides the first indication of the relative contribution of each gene and confirms that they account for the majority of PSACH and MED. Hum Mutat 33:144–157, 2012. © 2011 Wiley Periodicals, Inc.