A Novel Homozygous Variant of TMEM231 in a Case With Hypoplasia of the Cerebellar Vermis and Polydactyly

Abstract

Background: Transmembrane protein 231 (TMEM231) is a component of the B9 complex that participates in the formation of the diffusion barrier between the cilia and plasma membrane. Mutations in TMEM231 gene may contribute to the Joubert syndrome (JBTS) or Meckel–Gruber syndrome (MKS). However, reports on JBTS or MKS caused by TMEM231 mutations are comparatively rare.Method: We describe a Chinese fetus with unexplained hypoplasia of the cerebellar vermis and polydactyly, detected by ultrasound imaging. The fetus was primarily diagnosed with JBTS/MKS. The parents of this fetus were non-consanguineous and healthy. Whole-exome sequencing (WES) and bioinformatics strategies were employed to explore the genetic lesion of this family.Results: An unknown missense variant (c.19C>T;p.R7W) of TMEM231 gene was detected. The variant was predicted as pathogenic and was absent in our 200 healthy controls.Conclusion: WES was employed to explore the genetic lesion of a fetus with unexplained hypoplasia of the cerebellar vermis and polydactyly. A novel variant in TMEM231 gene was identified. Our study not only provided data for genetic counseling and prenatal diagnosis to this family but also broadened the spectrum of TMEM231 mutations.

Novel variants identified in five Chinese families with Joubert Syndrome: a case report

“…Prenatal screening accordingly becomes crucial, especially for families having a JS-related history. Routine prenatal ultrasound and fetal brain MRI can be used for early screening for cerebellar malformations, but they may not work well due to the inability to detect a typical MTS, which needs genetic tests to confirm the prenatal diagnosis [ 8 , 32 , 33 ]. Careful follow-up and rehabilitation training may enhance the patients’ daily activities for individuals who receive their diagnosis in the early stage of life.…”

Doubly bi-allelic variants of MTHFR and MTHFD1 in a Chinese patient with hyperhomocysteinemia and failure of folic acid therapy

“…The clinical data, including folate acid, vitamin B12 (VB12), ferritin, and erythropoietin (EPO), of each family member were collected for diagnosis or response evaluation. A total of 200 healthy subjects, as described in our previous study, were enrolled in this study to exclude polymorphisms ( Wang et al, 2021 ).…”

“…Exomes were captured using the SureSelect Human All Exon V6 kit (Agilent, Santa Clara, CA, United States), and next-generation sequencing was conducted using a HiSeq X Ten system (Illumina, San Diego, CA, United States). The strategies of data filtering and the necessary bioinformatics analyses can be referred to in the previous studies published by our laboratory group ( Fan et al, 2019 ; Wang et al, 2021 ).…”

Case report: Whole-exome sequencing identifies a novel DES mutation (p. E434K) in a Chinese family with cardiomyopathy and sudden cardiac death

“…Whole-exome sequencing yielded 11.7 Gb of data with 99.5% coverage of the target region and 99.1% of the target covered over 10 ×. Data quality control steps, co-segregation, and bioinformatics analysis were performed following the published literature and our previous published studies (8)(9)(10)(11). After preliminary screening, variants were further filtered by cardiomyopathy-related genes list as described in our previous study (12).…”