A monoallelic variant in EYA1 is associated with Branchio-Otic syndrome in a Malian family

Mol Genet Genomic Med. 2022 Jul;10(7):e1995. doi: 10.1002/mgg3.1995. Epub 2022 Jun 14.


Background: Branchio-otic syndrome (BO) is one of the most common types of syndromic hearing impairment (HI) with an incidence of 1/40,000 globally. It is an autosomal dominant disorder typically characterized by the coexistence of branchial cysts or fistulae, malformations of the external, middle, and inner ears with preauricular pits or tags and a variable degree of HI. Most cases of BO have been reported in populations of European ancestry. To date, only few cases have been reported in people from African descent.

Methods: After a careful clinical examination, a pure tone audiometry was performed. DNA was extracted from peripheral blood and whole exome, and Sanger sequencing were performed for genetic analysis.

Results: Eight individuals from a large non-consanguineous Malian family, with autosomal dominant inheritance were enrolled. The ages at diagnosis ranged from 8 to 54 years. A high phenotypic variability was noted among the affected individuals. Four patients presented with a post-lingual and mixed type of HI, one individual had conductive HI while three had normal hearing but presented other BO features namely branchial fistulae and preauricular sinus. Serum creatinine level and renal ultrasonography were normal in three affected individuals who performed them. Genetic testing identified a monoallelic pathogenic variant in EYA1 (c.1286A > G; p.Asp429Gly) segregating with BO syndrome in the family.

Conclusion: This is the first genetically confirmed case of BO syndrome caused by EYA1 variant in the sub-Saharan African population, expanding the genetic spectrum of the condition.

Keywords: EYA1; Africa; Branchio-otic syndrome; Mali; syndromic hearing impairment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Branchio-Oto-Renal Syndrome
  • Child
  • Hearing Loss* / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins* / genetics
  • Middle Aged
  • Nuclear Proteins* / genetics
  • Pedigree
  • Protein Tyrosine Phosphatases* / genetics
  • Young Adult


  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • EYA1 protein, human
  • Protein Tyrosine Phosphatases

Supplementary concepts

  • Branchiootic syndrome