Limb disorders

Gene: CD96

Comment on list classification: Leaving rating at red as only 1 reported case of a patient with limb abnormalities and a putative pathogenic variant in CD96

Created: 17 Oct 2018, 9:33 p.m.

CD96 is associated with C syndrome in OMIM and Gene2Phenotype (probable).

Kaname et al. (2007)(PMID:17847009) describe 2 unrelated patients with C syndrome. In the first the CD96 gene was interrupted in a de novo balanced translocation. The translocation breakpoint was located in exon 5 of CD96 and probably led to premature termination or loss of expression of CD96 protein. Semiquantitative RT-PCR analysis showed that CD96 expression in B cells of the patient was reduced to 45.8% of the normal level. However, in the clinical description of this patient (in PMID: 16835930) limb abnormalities are not described. In a second patient a missense mutation, T280M, in exon 6 of the CD96 gene was found (patient originally reported by Osaki et al. (2006)(PMID: 16528754). This patient had flexion deformity of the upper limb at the elbow, ulnarly deviated hands at the wrist joints, deep palmar creases, and talipes equinovalgus were evident. The fingers were short and tapering without poly‐ or syndactyly.

More recently Urreizti et al (2016)(PMID:26768331) screened CD96 and ASXL1 in a group of 11 individuals, 10 of them were diagnosed with OTCS (Opitz C syndrome) , and one had a BOS (Bohring-Opitz syndrome) phenotype. Only one putative pathogenic mutation was discovered in ASXL1 in the patient with BOS.

In summary, only 1 reported cases of a patient with limb abnormalities and a putative pathogenic variant in CD96 has been reported.

Created: 17 Oct 2018, 4:12 p.m.