title: 109 kb deletion of chromosome 4p16.3 in a patient with mild phenotype of Wolf-Hirschhorn syndrome.
abstract: Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome associated with growth retardation, developmental disabilities, epileptic seizures, and distinct facial features resulting from a deletion of the short arm of chromosome 4. The Wolf-Hirschhorn Syndrome Critical Region WHSCR2 includes the LETM1 gene and 5' end of the WHSC1 gene. A haploinsufficiency of WHSC1 is thought to be responsible for a number of WHS characteristics. We report on a 2-year-old male with severe growth retardation, microcephaly and a characteristic facial appearance. He had no internal anomalies and his developmental milestones were mildly delayed. An array-CGH analysis revealed loss of genomic copy numbers in the region 4p16.3, which included FGFR3, LETM1, and WHSC1. The size of the deletion was only 109 kb. The deletion included the important genes in WHSCR2. We suspect that haploinsufficiency of WHSC1 is the most probable cause of the growth deficiency, microcephaly, and characteristic facial features in WHS.
authors: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan. okamoto@osaka.email.ne.jp
authors: Nobuhiko
authors: N
authors: Okamoto
authors: Kazumi
authors: K
authors: Ohmachi
authors: Shino
authors: S
authors: Shimada
authors: Keiko
authors: K
authors: Shimojima
authors: Toshiyuki
authors: T
authors: Yamamoto
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics; D002675:Child, Preschool; D002872:Chromosome Deletion; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics; D005838:Genotype; D057895:Haploinsufficiency; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D054877:Wolf-Hirschhorn Syndrome / Q000175:diagnosis / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; C488528:LETM1 protein, human; D008565:Membrane Proteins; D012097:Repressor Proteins; D011495:Histone-Lysine N-Methyltransferase; C419586:NSD2 protein, human; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3