title: Clinical consequences in truncating mutations in exon 34 of NOTCH2: report of six patients with Hajdu-Cheney syndrome and a patient with serpentine fibula polycystic kidney syndrome.
abstract: It is debatable whether Hajdu-Cheney syndrome (HCS) and serpentine fibula-polycystic kidney syndrome (SFPKS) represent a single clinical entity with a variable degree of expression or two different entities, because both disorders share common clinical and radiological manifestations, including similar craniofacial characteristics, and defective bone mineralization. Since it was shown that heterozygous truncating mutations in NOTCH2 are responsible for both HCS and SFPKS, 37 patients with HCS and four patients with SFPKS are reported. To elucidate the clinical consequences of NOTCH2 mutations, we present detailed clinical information for seven patients with truncating mutations in exon 34 of NOTCH2, six with HCS and one with SFPKS. In addition, we review all the reported patients whose clinical manifestations are available. We found 13 manifestations including craniofacial features, acroosteolysis, Wormian bones, and osteoporosis in >75% of NOTCH2-positive patients. Acroosteolysis was observed in two patients with SFPKS and bowing fibulae were found in two patients with HCS. These clinical and molecular data would support the notion that HCS and SFPKS are a single disorder.
authors: Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan. ynarumi@shinshu-u.ac.jp
authors: Yoko
authors: Y
authors: Narumi
authors: Byung-Joo
authors: BJ
authors: Min
authors: Kenji
authors: K
authors: Shimizu
authors: Itsuro
authors: I
authors: Kazukawa
authors: Kiyoko
authors: K
authors: Sameshima
authors: Koichi
authors: K
authors: Nakamura
authors: Tomoki
authors: T
authors: Kosho
authors: Yumie
authors: Y
authors: Rhee
authors: Yoon-Sok
authors: YS
authors: Chung
authors: Ok-Hwa
authors: OH
authors: Kim
authors: Yoshimitsu
authors: Y
authors: Fukushima
authors: Woong-Yang
authors: WY
authors: Park
authors: Gen
authors: G
authors: Nishimura
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005091:Exons; D056726:Genetic Association Studies; D031845:Hajdu-Cheney Syndrome / Q000000981:diagnostic imaging* / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D011859:Radiography; D051883:Receptor, Notch2 / Q000235:genetics*; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; C497764:NOTCH2 protein, human; D051883:Receptor, Notch2