title: A novel NOTCH2 mutation identified in a Korean family with Hajdu-Cheney syndrome showing phenotypic diversity.
abstract: Hajdu-Cheney syndrome (HCS) and serpentine fibula-polycystic kidney syndrome (SFPKS) share many similarities, including craniofacial abnormalities, bony deformities, and renal involvement. Because mutations in exon 34 of NOTCH2 have been identified recently in both HCS and SFPKS patients, it has been suggested that these two syndromes be classed as the same disorder. A 3-year-old boy presented with polycystic kidneys and club feet detected during the fetal period; however, acroosteolysis and curved fibulae were not observed. His mother showed osteoporosis and had a history of compression fractures in the spine without renal anomalies. Although the same novel mutation in NOTCH2 was found in both the mother and her son, these patients displayed different clinical manifestations. In this report, we present a familial case of HCS in a boy and his mother that was suspected on physical examination and radiological findings. We speculate that HCS and SFPKS are a single disease entity with a wide spectrum of clinical manifestations associated with truncating mutations in exon 34 of NOTCH2.
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul.
authors.forename: Mi Seon
authors.initials: MS
authors.lastname: Han
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul jmko@snu.ac.kr.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Ko
authors.affiliation: Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Cho
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul.
authors.forename: Hae Il
authors.initials: HI
authors.lastname: Cheong
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D031845:Hajdu-Cheney Syndrome / Q000235:genetics* / Q000473:pathology*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy; D051883:Receptor, Notch2 / Q000235:genetics*; D056910:Republic of Korea; D017384:Sequence Deletion
chemical_list: C497764:NOTCH2 protein, human; D051883:Receptor, Notch2
keywords: Acroosteolysis; Hajdu–Cheney syndrome; NOTCH2; Osteoporosis; Serpentine fibula-polycystic kidney syndrome