2. Academic Validation
  3. A complex phenotype in a family with a pathogenic SOX3 missense variant

A complex phenotype in a family with a pathogenic SOX3 missense variant

  • Eur J Med Genet. 2018 Mar;61(3):168-172. doi: 10.1016/j.ejmg.2017.11.012.
Anne M Jelsig 1,  Birgitte R Diness 2,  Sven Kreiborg 3,  Katharina M Main 4,  Vibeke A Larsen 5,  Hanne Hove 2
Affiliations

Affiliations

  • 1 Department of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Electronic address: anne.marie.jelsig@regionh.dk.
  • 2 Department of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
  • 3 Department of Pediatric Dentistry and Clinical Genetics, School of Dentistry, University of Copenhagen, Copenhagen N, Denmark.
  • 4 Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Faculty of Health Sciences, Copenhagen, Denmark; International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Denmark.
  • 5 Department of Radiology, University of Copenhagen, Rigshospitalet, Denmark.
PMID: 29175558 DOI: 10.1016/j.ejmg.2017.11.012
Abstract

Duplications and deletions of Xq26-27 including SOX3 (Xq27.1) have been associated with X-linked mental retardation and isolated growth hormone deficiency (OMIM 300123) or X-linked panhypopituitarism (OMIM 312000). Yet, pathogenic point mutations seem to be extremely rare. We report a family with three affected males with several clinical features including mild intellectual disability, microphthalmia, coloboma, hypopituitarism, facial dysmorphology and dental anomalies, including microcephaly, retrognathia and a solitary median maxillary central incisor amongst Other features. Using Whole Exome Sequencing a missense variant in SOX3, NM_005634.2:c.449C>A; p.(Ser150Tyr) was identified. Segregation analysis in the family demonstrated that the variant was inherited through healthy females with its origin in the maternal grandmother showing germline mosaicism. Thus, we report one of the first cases of a pathogenic variant in SOX3 and germline mosaicism of this variant.

Keywords

Coloboma; Facial dysmorphology; Hypopituitarism; Microphthalmia; SOX3.

Figures