PT  - JOURNAL ARTICLE
AU  - Paul Kruszka
AU  - Dong Li
AU  - Margaret H Harr
AU  - Nathan R Wilson
AU  - Daniel Swarr
AU  - Elizabeth M McCormick
AU  - Rosetta M Chiavacci
AU  - Mindy Li
AU  - Ariel F Martinez
AU  - Rachel A Hart
AU  - Donna M McDonald-McGinn
AU  - Matthew A Deardorff
AU  - Marni J Falk
AU  - Judith E Allanson
AU  - Cindy Hudson
AU  - John P Johnson
AU  - Irfan Saadi
AU  - Hakon Hakonarson
AU  - Maximilian Muenke
AU  - Elaine H Zackai
TI  - Mutations in <em>SPECC1L</em>, encoding sperm antigen with calponin homology and coiled-coil domains 1-like, are found in some cases of autosomal dominant Opitz G/BBB syndrome
AID  - 10.1136/jmedgenet-2014-102677
DP  - 2015 Feb 01
TA  - Journal of Medical Genetics
PG  - 104--110
VI  - 52
IP  - 2
4099  - http://jmg.bmj.com/content/52/2/104.short
4100  - http://jmg.bmj.com/content/52/2/104.full
SO  - J Med Genet2015 Feb 01; 52
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.