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: Yoko Narumi, Byung-Joo Min, Kenji Shimizu, Itsuro Kazukawa, Kiyoko Sameshima, Koichi Nakamura, Tomoki Kosho, Yumie Rhee, Yoon-Sok Chung, Ok-Hwa Kim, Yoshimitsu Fukushima, Woong-Yang Park, Gen Nishimura
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 161A Issue 3 Pg. 518-26 (Mar 2013) ISSN: 1552-4833 [Electronic] United States
• PMID: 23401378 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Wiley Periodicals, Inc.

Chemical References

• Codon, Nonsense
• NOTCH2 protein, human
• Receptor, Notch2

Topics

• Adolescent
• Adult
• Child, Preschool
• Codon, Nonsense
• DNA Mutational Analysis
• Exons
• Genetic Association Studies
• Hajdu-Cheney Syndrome (diagnostic imaging, genetics)
• Humans
• Middle Aged
• Radiography
• Receptor, Notch2 (genetics)
• Young Adult