Confirmation that mutations in DDX59 cause an autosomal recessive form of oral-facial-digital syndrome: Further delineation of the DDX59 phenotype in two new families

• Published in: European journal of medical genetics 2017-10, Vol.60 (10), p.527-532
• Main Authors: Faily, Sara, Perveen, Rahat, Urquhart, Jill, Chandler, Kate, Clayton-Smith, Jill
• Format: Article
• Language: English
• Subjects: Adult; Child; Child, Preschool; Codon, Terminator - genetics; Female; Genes, Recessive; Humans; Infant; Male; Mutation; Orofaciodigital Syndromes - diagnosis; Orofaciodigital Syndromes - genetics; Pedigree; Phenotype; RNA Helicases - genetics
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2017.07.009

We report three probands from two unrelated consanguineous families of South Asian origin who all carry the same rare novel homozygous variant within the dead box helicase gene DDX59 in association with features of oral-facial-digital syndrome (OFDS). DDX59 variants have been reported previously in an unclassified, autosomal recessive form of OFDS; clinically associated with features including tongue lobulation, cleft palate, frontal bossing, hypertelorism and postaxial polydactyly. All three probands had lobulated tongues with tongue hamartomas, abnormal tongue tip, developmental delay and microcephaly, with just one proband demonstrating polydactlyly. The novel DDX59 variant was identified through autozygosity studies followed by sequencing of homozygous regions identified. It affects a stop codon, extending the protein product and is therefore predicted to be pathogenic. It is only the third reported DDX59 mutation associated with OFDS reported so far.