title: A novel nonsense GPSM2 mutation in a Yemeni family underlying Chudley-McCullough syndrome.
abstract: Mutations in the G Protein Signaling Modulator 2 (GPSM2) cause the autosomal recessive disorder Chudley-McCullough syndrome (CMS), which is characterized by profound congenital sensorineural hearing loss with various abnormalities in the brain. This phenotypic combination is attributed to the role played by GPSM2 in the establishment of planar polarity and spindle orientation during asymmetric cell divisions. Here we present two brothers from a Yemeni family who were diagnosed clinically with CMS then tested for GPSM2 mutations using Sanger sequencing. Consequent to sequencing, in silico tools (such as CADD) were utilized to assess functional consequences. Molecular analysis revealed a previously unreported homozygous mutation in GPSM2 in both brothers (c.1055C > A) leading to a truncating protein change; (p.Ser352*). This mutation is predicted to abolish all four GoLoco domains in GPSM2 and this explains the bioinformatic prediction for this mutation to be functionally damaging. Full clinical and molecular accounts of the novel mutation are provided in this paper.
authors.affiliation: Centre for Arab Genomic Studies, Dubai, United Arab Emirates. Electronic address: abdul.hamzeh@hmaward.org.ae.
authors.forename: Abdul Rezzak
authors.initials: AR
authors.lastname: Hamzeh
authors.affiliation: Centre for Arab Genomic Studies, Dubai, United Arab Emirates.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Nair
authors.affiliation: Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
authors.forename: Madiha
authors.initials: M
authors.lastname: Mohamed
authors.affiliation: Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
authors.forename: Fatima
authors.initials: F
authors.lastname: Saif
authors.affiliation: Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
authors.forename: Nafisa
authors.initials: N
authors.lastname: Tawfiq
authors.affiliation: Centre for Arab Genomic Studies, Dubai, United Arab Emirates.
authors.forename: Mahmoud Taleb
authors.initials: MT
authors.lastname: Al-Ali
authors.affiliation: Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
authors.forename: Fatma
authors.initials: F
authors.lastname: Bastaki
mesh_terms: D061085:Agenesis of Corpus Callosum / Q000235:genetics* / Q000473:pathology; D016080:Arachnoid Cysts / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology / Q000502:physiology*; D018389:Codon, Nonsense; D003198:Computer Simulation; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D010375:Pedigree; D015006:Yemen
chemical_list: D018389:Codon, Nonsense; C102754:GPSM2 protein, human; D047908:Intracellular Signaling Peptides and Proteins
keywords: DFNB82; G protein signalling modulator 2; LGN; PINS