LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Clinical variability at the mild end of BRAT1-related spectrum: evidence from two families with genotype-phenotype discordance.

Photo from academic.microsoft.com

Biallelic mutations in the BRAT1 gene, encoding BRCA1-associated ATM activator 1, result in variable phenotypes, from rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL) to neurodevelopmental disorder and cerebellar atrophy… Click to show full abstract

Biallelic mutations in the BRAT1 gene, encoding BRCA1-associated ATM activator 1, result in variable phenotypes, from rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL) to neurodevelopmental disorder and cerebellar atrophy with or without seizures (NEDCAS), without obvious genotype-phenotype associations. We describe two families at the mildest end of the spectrum, differing in clinical presentation despite a common genotype at BRAT1 locus. Two siblings displayed non-progressive congenital ataxia and shrunken cerebellum on MRI. A third unrelated patient showed normal neurodevelopment, adolescence-onset seizures and ataxia, shrunken cerebellum, and ultrastructural abnormalities on skin biopsy, representing the mildest form of NEDCAS hiterto described. Exome sequencing identified the c.638dup and the novel c.1395G>A BRAT1 variants, the latter causing exon 10 skipping. The p53-MCL test revealed normal ATM kinase activity. Our findings broaden the allelic and clinical spectrum of BRAT1-related disease, which should be suspected in presence of non-progressive cerebellar signs, even without a neurodevelopmental disorder. This article is protected by copyright. All rights reserved.

Keywords: clinical variability; brat1 related; genotype phenotype; two families; end; brat1

Journal Title: Human mutation
Year Published: 2021

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.