Two novel variants of the MBTPS1 gene in Czech family with Kondo-Fu type spondyloepiphyseal dysplasia and cataract
Abstract
Background: Only eight patients with biallelic pathogenic/likely pathogenic variants in MBTPS1 gene have been described to date. Six of them mainly present with Kondo-Fu type SED (spondyloepiphyseal dysplasia), remaining two are described to have presenile cataract, alopecia, oral muscular disorder and psoriasis-like phenotype (CAOD). Most of the affected individuals show growth restriction, SED and cataracts. Herein we present two affected siblings with novel variants in MBTPS1 gene.
Methods: Exome sequencing was performed in the older affected child and both healthy parents. Confirmation of the identified variants and segregation analysis were done using Sanger sequencing.
Results: The proband, a 7-year-old girl, suffered from prenatal growth failure, and her growth remains restricted. She has joint hypermobility, irregular ossification of femoral and tibial epiphyses and patella, bilateral congenital cataracts, and dysmorphic face with large protruding ears. Her brother, aged 4 months, was noted to have diaphragmatic hernia and hypotonia, in addition to poor growth. Due to his low age, dysmorphic features could not be reliably assessed. Two novel likely pathogenic variants in the MBTPS1 gene (NM_003791.4) c.163G>A and c.1022C>G in trans position were identified in both children. The first variant is predicted to impact splicing, while the second variant, p.(Pro341Arg) affects a very conserved amino acid in the peptidase domain.
Conclusion: The presented case extends the phenotypic spectrum of pathogenic variants in MBTPS1 and confirms that these can be linked to growth restriction as well as congenital cataracts.