mutations cause a novel cohesinopathy characterised by unspecific syndromic intellectual disability.

BACKGROUND

Cohesinopathies are rare neurodevelopmental disorders arising from a dysfunction in the cohesin pathway, which enables chromosome segregation and regulates gene transcription. So far, eight genes from this pathway have been reported in human disease. belongs to the STAG subunit of the core cohesin complex, along with five other subunits. This work aimed to identify the phenotype ascribed to mutations.

METHODS

Among patients referred for intellectual disability (ID) in genetics departments worldwide, array-comparative genomic hybridisation (CGH), gene panel, whole-exome sequencing or whole-genome sequencing were performed following the local diagnostic standards.

RESULTS

A mutation in was identified in 17 individuals from 16 families, 9 males and 8 females aged 2-33 years. Four individuals harboured a small microdeletion encompassing ; three individuals from two families had an intragenic deletion. Six deletions were identified by array-CGH, one by whole-exome sequencing. Whole-exome sequencing found de novo heterozygous missense or frameshift variants in eight patients, a panel of genes involved in ID identified a missense and a frameshift variant in two individuals. The 17 patients shared common facial features, with wide mouth and deep-set eyes. Four individuals had mild microcephaly, seven had epilepsy.

CONCLUSIONS

We report an international series of 17 individuals from 16 families presenting with syndromic unspecific ID that could be attributed to a deletion or point mutation. This first series reporting the phenotype ascribed to mutation in highlights the importance of data sharing in the field of rare disorders.