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| PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in seven Japanese patients with Noonan syndrome |
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| Author(s): Kosaki K, Suzuki T, Muroya K, Hasegawa T, Sato S, Matsuo N, Kosaki R, Nagai T, Hasegawa Y, Ogata T |
| Source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Volume: 87 Issue: 8 Pages: 3529-3533 Published: AUG 2002 |
| Times Cited: 53 References: 29 |
| Abstract: Noonan syndrome is an autosomal dominant disorder defined by short stature, delayed puberty, and characteristic dysmorphic features. Tartaglia et al. (Nature Genetics, 29:465-468) have recently shown that gain-of-function mutations in the gene PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) cause Noonan syndrome in roughly half of patients that they examined. To further explore the relevance of PTPN11 mutations to the pathogenesis of Noonan syndrome, we analyzed the PTPN11 gene in 21 Japanese patients. Mutation analysis of the 15 coding exons and their flanking introns by denaturing HPLC and direct sequencing revealed six different heterozygous missense mutations (Asp61Gly, Tyr63Cys, Ala72Ser, Thr73Ile, Phe285Ser, and Asn308Asp) in seven cases (six sporadic and one familial). The mutations clustered either in the N-Src homology 2 domain or in the protein-tyrosine phosphatase domain. The clinical features of the mutation-positive and mutation-negative patients were comparable. The results provide further support to the notion that PTPN11 mutations are responsible for the development of Noonan syndrome in a substantial fraction of patients and that relatively infrequent features of Noonan syndrome, such as sensory deafness and bleeding diathesis, can also result from mutations of PTPN11. |
| Document Type: Article |
| Language: English |
| Reprint Address: Ogata, T (reprint author), Keio Univ, Sch Med, Dept Pediat, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan |
Addresses:
1. Keio Univ, Sch Med, Dept Pediat, Shinjuku Ku, Tokyo 1608582, Japan
2. Keio Univ, Sch Med, Pharm Fund Growth & Dev, Tokyo 1608582, Japan
3. Ichikawa Gen Hosp, Tokyo Dent Coll, Dept Pediat, Ichikawa 2520853, Japan
4. Natl Childrens Hosp, Tokyo 1548509, Japan
5. Dokkyo Univ, Koshigaya Hosp, Sch Med, Dept Pediat, Koshigaya 3430845, Japan
6. Tokyo Metropolitan Kiyose Childrens Hosp, Div Endocrinol & Metab, Kiyose 2048567, Japan
7. Tokyo Elect Power Co Hosp, Dept Pediat, Tokyo 1600016, Japan |
| Publisher: ENDOCRINE SOC, 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA |
| Subject Category: Endocrinology & Metabolism |
| IDS Number: 581HG |
| ISSN: 0021-972X |
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