Identification of a novel splice mutation in CTNNB1 gene in a Chinese family with both severe intellectual disability and serious visual defects

Abstract

The CTNNB1 gene encode the β-catenin protein which is a core unit of the cadherin/catenin multiprotein complex. The loss-of-function mutation of the CTNNB1 gene recently has been confirmed as a cause of intellectual disability. Previous studies have found that patients with CTNNB1 gene mutation may have other clinical manifestation such as microcephaly, abnormal facial features, motor and language delays, and mild visual defects. Here, we reported a 27-year-old Chinese pregnant woman with a severe intellectual disability and serious visual defects who was detected with a novel splice mutation (c.734+1G>A) in CTNNB1 gene by whole-exome sequencing and confirmed by Sanger sequencing. Further investigation showed that the variant was inherited from her mother with similar phenotypes. This report not only helps to expand the mutant spectrum of the CTNNB1 gene but also prompts a new insight into genetic diagnosis in patients with both serious intellectual disability and visual defects. Electronic supplementary material The online version of this article (10.1007/s10072-019-03823-5) contains supplementary material, which is available to authorized users.

Case Report: A de novo CTNNB1 Nonsense Mutation Associated With Neurodevelopmental Disorder, Retinal Detachment, Polydactyly

“…The patient we reported was similar to the previous reports, but the polydactyly was not reported in the previous cases, and retinal detachment was also rare in the previous case reports, only two cases in the Asian population reported with retinal detachment (8,10). However, the mutations of the CTNNB1 were different from each other among the three patients.…”

“…Spasticity may also occur in the affected individuals, particularly of the lower extremities, and may have behavioral abnormalities (4). At present, 33 cases of the disease have been reported in the world (2,(5)(6)(7)(8)(9)(10)(11), with only two in Asia (8,10). This paper reports the clinical characteristics and genetic analysis of the third case of neurodevelopmental disorder caused by CTNNB1 gene mutation in the Asian population, and we found that polydactyly may be a new feature of CTNNB1 mutation.…”

Role of NDP- and FZD4-Related Novel Mutations Identified in Patients with FEVR in Norrin/β-Catenin Signaling Pathway

“…So far, there have been at least nine genes attributed to the progression of FEVR including NDP [26], FZD4 [27], LRP5 [28], TSPAN12 [29], ZNF408 [30], KIF11 [31], RCBTB1 [32], CTNNB1 [33], and JAG1 [34]. Our previous results also provided insight into the relationship between a novel splicing mutation (c.734+1G>A) in CTNNB1 and a 27-year-old Chinese pregnant woman with a severe intellectual disability and FEVR [35]. Human FEVR displays variable ocular defects and serves as an excellent model to explore Wnt signaling, especially causing mutations in NDP, FZD4, LRP5, and TSPAN12.…”

<p>A de novo <em>CTNNB1</em> Novel Splice Variant in an Adult Female with Severe Intellectual Disability</p>

“…This specific variant in the CTNNB1 gene has not been described before in the literature, but another variant of the same splice donor site was reported in 2019 in a patient with both severe ID and visual defects. 6 The de novo CTNNB1 splice variant is considered to be causative for the severe ID and the clinical phenotype of the patient and is corresponding with a diagnosis of NEDSDV without, however, the vitreoretinopathy.…”

“…2 So far, 35 patients have been reported with a (de novo) loss-of-function variant of CTNNB1. [1][2][3][4][5][6] In two other patients, a deletion comprising the full gene was found. 3,7 Four out of this total of 37 patients were of adult age (27, 27, 29, and 51 years) while the majority were infant or adolescent (age range: 0-20 years).…”