title: Causative novel PNKP mutations and concomitant PCDH15 mutations in a patient with microcephaly with early-onset seizures and developmental delay syndrome and hearing loss.
abstract: We report on a 1-year-old boy with microcephaly with a simplified gyral pattern, early-onset seizures, congenital hearing loss and a severe developmental delay. Trio-based whole-exome sequencing identified candidate compound heterozygous mutations in two genes: c.163G>T (p.Ala55Ser) and c.874G>A (p.Gly292Arg) in polynucleotide kinase 3'-phosphatase gene (PNKP), and c.195G>A (p.Met65Ile) and c.1210A>C (p.Ser404Arg) in PCDH15. PNKP and PCDH15 mutations have been reported in autosomal recessive microcephaly with early-onset seizures and developmental delay syndrome, and Usher syndrome type 1F, respectively. Our patient showed neurological features similar to reported cases of both syndromes that could be explained by the observed mutations in both PNKP and PCDH15, which therefore appear to be pathogenic in this case.
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Mitsuko
authors: M
authors: Nakashima
authors: 1] Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan [2] Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
authors: Kyoko
authors: K
authors: Takano
authors: 1] Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan [2] Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
authors: Hitoshi
authors: H
authors: Osaka
authors: Department of Radiology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors: Noriko
authors: N
authors: Aida
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Yoshinori
authors: Y
authors: Tsurusaki
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Noriko
authors: N
authors: Miyake
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Hirotomo
authors: H
authors: Saitsu
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Naomichi
authors: N
authors: Matsumoto
mesh_terms: D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D034381:Hearing Loss / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D012640:Seizures / Q000235:genetics*; D017422:Sequence Analysis, DNA; D052245:Usher Syndromes / Q000235:genetics
chemical_list: C498835:CDHR15, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; C530380:PNKP protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); D045643:DNA Repair Enzymes