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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.

Authors:
Paul Kruszka Dong Li Margaret H Harr Nathan R Wilson Daniel Swarr Elizabeth M McCormick Rosetta M Chiavacci Mindy Li Ariel F Martinez Rachel A Hart Donna M McDonald-McGinn Matthew A Deardorff Marni J Falk Judith E Allanson Cindy Hudson John P Johnson Irfan Saadi Hakon Hakonarson Maximilian Muenke Elaine H Zackai

J Med Genet 2015 Feb 20;52(2):104-10. Epub 2014 Nov 20.

Division of Human Genetics, The Children's Hospital of Philadelphia, Clinical Genetics Center, and the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

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.

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http://dx.doi.org/10.1136/jmedgenet-2014-102677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393015PMC
February 2015

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