| Autor: |
Schwartzmann, Sarina, Zhao, Max, Sczakiel, Henrike Lisa, Hildebrand, Gabriele, Ehmke, Nadja, Horn, Denise, Mensah, Martin A., Boschann, Felix |
| Zdroj: |
American Journal of Medical Genetics. Part A; Jul2024, Vol. 194 Issue 7, p1-7, 7p |
| Abstrakt: |
Pathogenic variants in TRIO, encoding the guanine nucleotide exchange factor, are associated with two distinct neurodevelopmental delay phenotypes: gain‐of‐function missense mutations within the spectrin repeats are causative for a severe developmental delay with macrocephaly (MIM: 618825), whereas loss‐of‐function missense variants in the GEF1 domain and truncating variants throughout the gene lead to a milder developmental delay and microcephaly (MIM: 617061). In three affected family members with mild intellectual disability/NDD and microcephaly, we detected a novel heterozygous TRIO variant at the last coding base of exon 31 (NM_007118.4:c.4716G>A). RNA analysis from patient‐derived lymphoblastoid cells confirmed aberrant splicing resulting in the skipping of exon 31 (r.4615_4716del), leading to an in‐frame deletion in the first Pleckstrin homology subdomain of the GEF1 domain: p.(Thr1539_Lys1572del). To test for a distinct gestalt, facial characteristics of the family members and 41 previously published TRIO cases were systematically evaluated via GestaltMatcher. Computational analysis of the facial gestalt suggests a distinguishable facial TRIO‐phenotype not outlined in the existing literature. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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