Novel loss-of-function variants in TRIO are associated with neurodevelopmental disorder: case report

• Main Authors: Laura Schultz-Rogers, Karthik Muthusamy, Filippo Pinto e Vairo, Eric W. Klee, Brendan Lanpher
• Format: Article
• Language: English
• Published: BMC 2020-11-01
• Series: BMC Medical Genetics
• Subjects: TRIO gene; Autism; Macrocephaly; Microcephaly; Cutis aplasia
• Online Access: http://link.springer.com/article/10.1186/s12881-020-01159-y

Abstract Background Damaging variants in TRIO have been associated with moderate to severe neurodevelopmental disorders in humans. While recent work has delineated the positional effect of missense variation on the resulting phenotype, the clinical spectrum associated with loss-of-function variation has yet to be fully defined. Case presentation We report on two probands with novel loss-of-function variants in TRIO. Patient 1 presents with a severe neurodevelopmental disorder and macrocephaly. The TRIO variant is inherited from his affected mother. Patient 2 presents with moderate developmental delays, microcephaly, and cutis aplasia with a frameshift variant of unknown inheritance. Conclusions We describe two patients with neurodevelopmental disorder, macro/microcephaly, and cutis aplasia in one patient. Both patients have loss-of-function variants, helping to further characterize how these types of variants affect the phenotypic spectrum associated with TRIO. We also present the third reported case of autosomal dominant inheritance of a damaging variant in TRIO.