RT Journal Article SR Electronic T1 Expanding the clinical spectrum of recessive truncating mutations of KLHL7 to a Bohring-Opitz-like phenotype JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP jmedgenet-2017-104748 DO 10.1136/jmedgenet-2017-104748 A1 Ange-Line Bruel A1 Stefania Bigoni A1 Joanna Kennedy A1 Margo Whiteford A1 Chris Buxton A1 Giulia Parmeggiani A1 Matt Wherlock A1 Geoff Woodward A1 Mark Greenslade A1 Maggie Williams A1 Judith St-Onge A1 Alessandra Ferlini A1 Giampaolo Garani A1 Elisa Ballardini A1 Bregje W van Bon A1 Rocio Acuna-Hidalgo A1 Axel Bohring A1 Jean-François Deleuze A1 Anne Boland A1 Vincent Meyer A1 Robert Olaso A1 Emmanuelle Ginglinger A1 DDD Study A1 Jean-Baptiste Rivière A1 Han G Brunner A1 Alexander Hoischen A1 Ruth Newbury-Ecob A1 Laurence Faivre A1 Christel Thauvin-Robinet A1 Julien Thevenon YR 2017 UL http://jmg.bmj.com/content/early/2017/10/26/jmedgenet-2017-104748.abstract AB Background Bohring-Opitz syndrome (BOS) is a rare genetic disorder characterised by a recognisable craniofacial appearance and a typical ‘BOS’ posture. BOS is caused by sporadic mutations ofASXL1. However, several typical patients with BOS have no molecular diagnosis, suggesting clinical and genetic heterogeneity.Objectives To expand the phenotypical spectrum of autosomal recessive variants of KLHL7, reported as causing Crisponi syndrome/cold-induced sweating syndrome type 1 (CS/CISS1)-like syndrome.Methods We performed whole-exome sequencing in two families with a suspected recessive mode of inheritance. We used the Matchmaker Exchange initiative to identify additional patients.Results Here, we report six patients with microcephaly, facial dysmorphism, including exophthalmos, nevus flammeus of the glabella and joint contractures with a suspected BOS posture in five out of six patients. We identified autosomal recessive truncating mutations in the KLHL7 gene. KLHL7 encodes a BTB–kelch protein implicated in the cell cycle and in protein degradation by the ubiquitin–proteasome pathway. Recently, biallelic mutations in the KLHL7 gene were reported in four families and associated with CS/CISS1, characterised by clinical features overlapping with our patients.Conclusion We have expanded the clinical spectrum of KLHL7 autosomal recessive variants by describing a syndrome with features overlapping CS/CISS1 and BOS.