Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) initially diagnosed as ALG6-CDG: Functional evidence for benignity of the ALG6 c.391T>C (p.Tyr131His) variant and further expanding the BBSOAS phenotype

Rodrigo Tzovenos Starosta, Jessica Tarnowski, Filippo Pinto e. Vairo, Kimiyo Raymond, Graeme Preston, Eva Morava

Research output: Contribution to journalArticle

Abstract

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a recently described autosomal dominant syndrome of developmental delay, cortical vision loss with optic nerve atrophy, epilepsy, and autism spectrum disorder. Due to its many overlapping features with congenital disorders of glycosylation (CDG), the differential diagnosis between these disorders may be difficult and relies on molecular genetic testing. We report on a 31-year-old female initially diagnosed with ALG6-CDG based on glycosylation abnormalities on transferrin isoelectrofocusing and targeted genetic testing, and later diagnosed with BBSOAS by whole-exome sequencing (WES). Functional studies on cultured fibroblasts including Western blotting and RT-qPCR, as well as mass spectrometry of glycosylated transferrin and MALDI-TOF glycan analysis in serum, demonstrated normal glycosylation in this patient. In this report, we extend the phenotype of BBSOAS with ataxia and protein-losing enteropathy. This case is illustrative of the utility of whole exome sequencing in the diagnostic odyssey, and the potential pitfalls of relying on focused genetic testing results for diagnosis of conditions with complex overlapping phenotypes.

Original languageEnglish (US)
Article number103941
JournalEuropean Journal of Medical Genetics
Volume63
Issue number7
DOIs
StatePublished - Jul 2020

Keywords

  • Autism spectrum disease
  • CDG
  • Protein-losing enteropathy
  • Seizure
  • Transient ataxia
  • Visual loss

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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