TY - JOUR T1 - Expanding the clinical spectrum of recessive truncating mutations of <em>KLHL7</em> to a Bohring-Opitz-like phenotype JF - Journal of Medical Genetics JO - J Med Genet DO - 10.1136/jmedgenet-2017-104748 SP - jmedgenet-2017-104748 AU - Ange-Line Bruel AU - Stefania Bigoni AU - Joanna Kennedy AU - Margo Whiteford AU - Chris Buxton AU - Giulia Parmeggiani AU - Matt Wherlock AU - Geoff Woodward AU - Mark Greenslade AU - Maggie Williams AU - Judith St-Onge AU - Alessandra Ferlini AU - Giampaolo Garani AU - Elisa Ballardini AU - Bregje W van Bon AU - Rocio Acuna-Hidalgo AU - Axel Bohring AU - Jean-François Deleuze AU - Anne Boland AU - Vincent Meyer AU - Robert Olaso AU - Emmanuelle Ginglinger AU - DDD Study AU - Jean-Baptiste Rivière AU - Han G Brunner AU - Alexander Hoischen AU - Ruth Newbury-Ecob AU - Laurence Faivre AU - Christel Thauvin-Robinet AU - Julien Thevenon Y1 - 2017/10/26 UR - http://jmg.bmj.com/content/early/2017/10/26/jmedgenet-2017-104748.abstract N2 - 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. ER -