RT Journal Article SR Electronic T1 Mutations in SPECC1L, encoding sperm antigen with calponin homology and coiled-coil domains 1-like, are found in some cases of autosomal dominant Opitz G/BBB syndrome JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 104 OP 110 DO 10.1136/jmedgenet-2014-102677 VO 52 IS 2 A1 Paul Kruszka A1 Dong Li A1 Margaret H Harr A1 Nathan R Wilson A1 Daniel Swarr A1 Elizabeth M McCormick A1 Rosetta M Chiavacci A1 Mindy Li A1 Ariel F Martinez A1 Rachel A Hart A1 Donna M McDonald-McGinn A1 Matthew A Deardorff A1 Marni J Falk A1 Judith E Allanson A1 Cindy Hudson A1 John P Johnson A1 Irfan Saadi A1 Hakon Hakonarson A1 Maximilian Muenke A1 Elaine H Zackai YR 2015 UL http://jmg.bmj.com/content/52/2/104.abstract AB Background Opitz G/BBB syndrome is a heterogeneous disorder characterised by variable expression of midline defects including cleft lip and palate, hypertelorism, laryngealtracheoesophageal anomalies, congenital heart defects, and hypospadias. The X-linked form of the condition has been associated with mutations in the MID1 gene on Xp22. The autosomal dominant form has been linked to chromosome 22q11.2, although the causative gene has yet to be elucidated. Methods and results In this study, we performed whole exome sequencing on DNA samples from a three-generation family with characteristics of Opitz G/BBB syndrome with negative MID1 sequencing. We identified a heterozygous missense mutation c.1189A>C (p.Thr397Pro) in SPECC1L, located at chromosome 22q11.23. Mutation screening of an additional 19 patients with features of autosomal dominant Opitz G/BBB syndrome identified a c.3247G>A (p.Gly1083Ser) mutation segregating with the phenotype in another three-generation family. Conclusions Previously, SPECC1L was shown to be required for proper facial morphogenesis with disruptions identified in two patients with oblique facial clefts. Collectively, these data demonstrate that SPECC1L mutations can cause syndromic forms of facial clefting including some cases of autosomal dominant Opitz G/BBB syndrome and support the original linkage to chromosome 22q11.2.