Dual molecular diagnosis due to heterozygous variants in ZMYDN11 and ATP2B1

Ehmke, N. (2024). Dual molecular diagnosis due to heterozygous variants in ZMYDN11 and ATP2B1 (Version 1) [DataSet]. GestaltMatcher Database.

We present the case of a 15-year-old patient with mild intellectual disability and behavioural abnormalities. He achieved the milestones of psychomotor development late and had muscular hypotonia in early childhood. He attends a special needs school and has limited reading and writing skills. He lives with a foster family and has been reported to exhibit aggressive outbursts. Physical examination revealed hypertelorism, long palpebral fissures, full lips and thick, curly hair. Chromosome analysis, array CGH and FMR1 repeat diagnostics were unremarkable. Exome analysis identified two rare heterozygous variants. The first was a frameshift variant in ZMYND11 (NM001370100.5:c.13171320del;p.(Thr440fs3)), which has previously been reported in patients with an autosomal dominant intellectual disability disorder (MRD30, MIM:616083). The second variant was a nonsense variant in the ATP2B1 gene (NM_001366521.1:c.2959G>T;p.(Glu987)), which, to our knowledge, has not yet been reported in the literature. However, comparable nonsense variants have been described as the cause of an autosomal dominant developmental disorder (MRD66, MIM:619910). Segregation analysis was not possible.