Combined exome and whole transcriptome sequencing identifies a de novo intronic SRCAPvariant causing DEHMBA syndrome with severe sleep disorder

Autor: Morlino, Silvia, Vaccaro, Lorenzo, Leone, Maria Pia, Nardella, Grazia, Bisceglia, Luigi, Ortore, Rocco Pio, Verzicco, Giannandrea, Cassano, Lazzaro, Castori, Marco, Cacchiarelli, Davide, Micale, Lucia
Zdroj: Journal of Human Genetics; June 2024, Vol. 69 Issue: 6 p287-290, 4p
Abstrakt: Rare heterozygous variants in exons 33-34 of the SRCAPgene are associated with Floating-Harbor syndrome and have a dominant-negative mechanism of action. At variance, heterozygous nullalleles falling in other parts of the same gene cause developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (DEHMBA) syndrome. We report an 18-year-old man with DEHMBA syndrome and obstructive sleep apnea, who underwent exome sequencing (ES) and whole transcriptome sequencing (WTS) on peripheral blood. Trio analysis prioritized the de novo heterozygous c.5658+5 G > A variant. WTS promptly demostrated four different abnormal transcripts affecting >40% of the reads, three of which leading to a frameshift. This study demonstrated the efficacy of a combined ES-WTS approach in solving undiagnosed cases. We also speculated that sleep respiratory disorder may be an underdiagnosed complication of DEHMBA syndrome.
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