Severe microcephaly
Gene: TPR
Comment on classification of this gene: This gene should be added with a RED rating as the association of TPR to microcephaly is based on biallelic variants identified from a report of two siblings.
Two siblings harbouring variants c.6625C>T/ p.Arg2209Ter (identified in heterozygous state in both siblings and father) and c.2610 + 5G > A (identified in heterozygous state in both siblings and mother) were reported with ataxia, microcephaly and severe intellectual disability. The occipitofrontal circumference (OFC) was at 3rd centile for individual 1 and at 10th centile for individual 2 and dropped to below 1st centile at eight months and five months respectively.
Functional analyses in patient fibroblasts provide evidence that the variants affect TPR splicing, reduce steady-state TPR levels, abnormal nuclear pore composition and density, and altered global RNA distribution.
This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: LiteratureCreated: 12 Dec 2022, 10:46 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Microcephaly, MONDO:0001149
Publications
gene: TPR was added gene: TPR was added to Severe microcephaly. Sources: Literature Mode of inheritance for gene: TPR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TPR were set to 34494102 Phenotypes for gene: TPR were set to Microcephaly, MONDO:0001149 Review for gene: TPR was set to RED