title: Association Between Invisible Basal Ganglia and ZNF335 Mutations: A Case Report.
abstract: ZNF335 was first reported in 2012 as a causative gene for microcephaly. Because only 1 consanguineous pedigree has ever been reported, the key clinical features associated with ZNF335 mutations remain unknown. In this article, we describe another family harboring ZNF335 mutations. The female proband was the first child of nonconsanguineous Japanese parents. At birth, microcephaly was absent; her head circumference was 32.0 cm (-0.6 SD). At 3 months, microcephaly was noted, (head circumference, 34.0 cm [-4.6 SD]). Brain MRI showed invisible basal ganglia, cerebral atrophy, brainstem hypoplasia, and cerebellar atrophy. At 33 months, (head circumference, 41.0 cm [-5.1 SD]), she had severe psychomotor retardation. After obtaining informed consent from her parents, we performed exome sequencing in the proband and identified 1 novel and 1 known mutation in ZNF335, namely, c.1399T>C (p.C467R) and c.1505A>G (p.Y502C), respectively. The mutations were individually transmitted by her parents, indicating that the proband was compound heterozygous for the mutations. Her brain imaging findings, including invisible basal ganglia, were similar to those observed in the previous case with ZNF335 mutations. We speculate that invisible basal ganglia may be the key feature of ZNF335 mutations. For infants presenting with both microcephaly and invisible basal ganglia, ZNF335 mutations should be considered as a differential diagnosis.
authors.affiliation: Department of Pediatrics, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan;
authors.forename: Rieko
authors.initials: R
authors.lastname: Sato
authors.affiliation: Department of Pediatrics, Yachiyo Medical Center, Tokyo Women's Medical University, Yachiyo, Japan;
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Takanashi
authors.affiliation: Department of Child Neurology, Kanagawa Children's Medical Center, Yokohama, Japan;
authors.forename: Yu
authors.initials: Y
authors.lastname: Tsuyusaki
authors.affiliation: Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan; Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan; and.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan; ttakahashi@keio.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D001284:Atrophy; D001479:Basal Ganglia / Q000002:abnormalities*; D001921:Brain / Q000473:pathology; D001933:Brain Stem / Q000002:abnormalities; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007564:Japan; D008279:Magnetic Resonance Imaging; D008831:Microcephaly / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D011596:Psychomotor Disorders / Q000209:etiology; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C466083:ZNF335 protein, human