Temple syndrome: comprehensive molecular and clinical findings in 32 Japanese patients

• Published in: Genetics in medicine Vol. 19; no. 12; pp. 1356 - 1366
• Main Authors: Kagami, Masayo, Nagasaki, Keisuke, Kosaki, Rika, Horikawa, Reiko, Naiki, Yasuhiro, Saitoh, Shinji, Tajima, Toshihiro, Yorifuji, Tohru, Numakura, Chikahiko, Mizuno, Seiji, Nakamura, Akie, Matsubara, Keiko, Fukami, Maki, Ogata, Tsutomu
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2017; Elsevier Limited; Nature Publishing Group
• Subjects: 631/208/2489/2487; 692/699/2743/1530; 692/700/139/1512; 692/700/478/174; Adolescent; Adult; Biomedical and Life Sciences; Biomedicine; Child; Child, Preschool; Chromosome Aberrations; Chromosome Disorders - diagnosis; Chromosome Disorders - genetics; Chromosomes, Human, Pair 14; Facies; Female; Genetic Association Studies; Genetic Testing; Genomic Imprinting; Growth Charts; Human Genetics; Humans; Infant; Japan; Laboratory Medicine; Male; Middle Aged; Original; original-research-article; Phenotype; Physical growth; Pregnancy; Puberty; Young Adult; clinical diagnosis; epimutation; UPDmat; Temple syndrome; microdeletion
• ISSN: 1098-3600; 1530-0366; 1530-0366
• DOI: 10.1038/gim.2017.53

Purpose Temple syndrome (TS14) is a rare imprinting disorder caused by aberrations at the 14q32.2 imprinted region. Here, we report comprehensive molecular and clinical findings in 32 Japanese patients with TS14. Methods We performed molecular studies for TS14 in 356 patients with variable phenotypes, and clinical studies in all TS14 patients, including 13 previously reported. Results We identified 19 new patients with TS14, and the total of 32 patients was made up of 23 patients with maternal uniparental disomy (UPD(14)mat), six patients with epimutations, and three patients with microdeletions. Clinical studies revealed both Prader-Willi syndrome (PWS)-like marked hypotonia and Silver-Russell syndrome (SRS)-like phenotype in 50% of patients, PWS-like hypotonia alone in 20% of patients, SRS-like phenotype alone in 20% of patients, and nonsyndromic growth failure in the remaining 10% of patients in infancy, and gonadotropin-dependent precocious puberty in 76% of patients who were pubescent or older. Conclusion These results suggest that TS14 is not only a genetically diagnosed entity but also a clinically recognizable disorder. Genetic testing for TS14 should be considered in patients with growth failure plus both PWS-like hypotonia and SRS-like phenotypes in infancy, and/or precocious puberty, as well as a familial history of Kagami-Ogata syndrome due to maternal microdeletion at 14q32.2.