title: A Novel Missense Mutation in the CLPP Gene Causing Perrault Syndrome Type 3 in a Turkish Family.
abstract: Perrault syndrome (PRLTS) is a heterogeneous group of clinical and genetic disorders characterized by sensory neuronal hearing loss in both sexes and premature ovarian failure or infertility in females. Neurological and hearing loss symptoms appear early in life, but female infertility cannot be detected before puberty. Spastic limbs, muscle weakness, delayed puberty and irregular menstrual cycles have also been observed in PRLTS patients. Mutations in five genes, i.e. HSD17B4, HARS2, CLPP, LARS2, and C10orf2, have been reported in five subtypes of PRLTS. Here, we report a milder phenotype of PRLTS in a Turkish family in which two affected patients had no neurological findings. However, both were characterized by sensory neuronal hearing loss and the female sibling had secondary amenorrhea and gonadal dysgenesis. Genome-wide homozygosity mapping using 300K single-nucleotide polymorphism microarray analysis together with iScan platform (Illumina, USA) followed by candidate gene Sanger sequencing with ABI 3500 Genetic Analyzer (Life Technologies, USA) were used for molecular diagnosis. We found a novel missense alteration c.624C>G; p.Ile208Met in exon 5 of the CLPP at chromosome 19p13.3. This study expands the mutation spectrum of CLPP pathogenicity in PRLTS type 3 phenotype.
authors.forename: Fatma
authors.initials: F
authors.lastname: Dursun
authors.forename: Hussein Sheikh Ali
authors.initials: HS
authors.lastname: Mohamoud
authors.forename: Noreen
authors.initials: N
authors.lastname: Karim
authors.forename: Muhammad
authors.initials: M
authors.lastname: Naeem
authors.forename: Musharraf
authors.initials: M
authors.lastname: Jelani
authors.affiliation: Ümraniye Training and Research Hospital, Clinic of Pediatric Endocrinology, İstanbul, Turkey, Phone: +90 216 632 18 18 E-mail: heveskirmizibekmez@yahoo.com.
authors.forename: Heves
authors.initials: H
authors.lastname: Kırmızıbekmez
mesh_terms: D000293:Adolescent; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D049071:Endopeptidase Clp / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D005838:Genotype; D023961:Gonadal Dysgenesis, 46,XX / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014421:Turkey; D055815:Young Adult
chemical_list: C568646:ClpP protein, human; D049071:Endopeptidase Clp