2. Academic Validation
  3. 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

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

  • J Med Genet. 2015 Feb;52(2):104-10. doi: 10.1136/jmedgenet-2014-102677.
Paul Kruszka 1,  Dong Li 2,  Margaret H Harr 3,  Nathan R Wilson 4,  Daniel Swarr 3,  Elizabeth M McCormick 3,  Rosetta M Chiavacci 2,  Mindy Li 3,  Ariel F Martinez 1,  Rachel A Hart 1,  Donna M McDonald-McGinn 3,  Matthew A Deardorff 3,  Marni J Falk 3,  Judith E Allanson 5,  Cindy Hudson 6,  John P Johnson 7,  Irfan Saadi 4,  Hakon Hakonarson 2,  Maximilian Muenke 1,  Elaine H Zackai 3
Affiliations

Affiliations

  • 1 Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • 2 The Center for Applied Genomics, The Children's Hospital of Philadelphia, and the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • 3 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.
  • 4 Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA.
  • 5 Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
  • 6 Shodair Children's Hospital, Helena, Montana, USA.
  • 7 Shodair Children's Hospital, Helena, Montana, USA Clinical Genetics and Metabolism, Floating Hospital for Children, Tufts Medical Center, Boston, Massachusetts, USA.
PMID: 25412741 DOI: 10.1136/jmedgenet-2014-102677
Abstract

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.

Keywords

Clinical genetics; Developmental; Diagnosis; Genetics.

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