| Full text | |
| Author(s): |
Bertola, Debora R.
[1, 2]
;
Yamamoto, Guilherme L.
[1, 2]
;
Almeida, Tatiana F.
[1]
;
Buscarilli, Michelle
[2]
;
Jorge, Alexander A. L.
[3]
;
Malaquias, Alexsandra C.
[3]
;
Kim, Chong A.
[2]
;
Takahashi, Vanessa N. V.
[1]
;
Passos-Bueno, Maria Rita
[1]
;
Pereira, Alexandre C.
[4]
Total Authors: 10
|
| Affiliation: | [1] Univ Sao Paulo, Inst Biociencias, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med, Hosp Clin, Unidade Genet, Inst Crianca, Sao Paulo - Brazil
[3] Univ Sao Paulo, Fac Med, Sao Paulo - Brazil
[4] Univ Sao Paulo, Fac Med, Hosp Clin, Inst Coracao, Sao Paulo - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | AMERICAN JOURNAL OF MEDICAL GENETICS PART A; v. 164, n. 11, p. 2952-2957, NOV 2014. |
| Web of Science Citations: | 28 |
| Abstract | |
Noonan syndrome (NS) is an autosomal dominant disorder consisting of short stature, short and/or webbed neck, distinctive facial features, cardiac abnormalities, cryptorchidism, and coagulation defects. NS exhibits genetic heterogeneity, associated with mutated genes that participate in RAS-mitogen-activated protein kinase signal transduction. Recently, a new gene (RIT1) was discovered as the causative gene in 17 of 180 Japanese individuals who were negative for the previously known genes for NS and were studied using exome sequencing (four patients), followed by Sanger sequencing (13 patients). The present study used the same technique in 70 Brazilian patients with NS and identified six with RIT1 missense mutations. Thus, we confirm that RIT1 is responsible for approximately 10% of the patients negative for mutations in the previously known genes. The phenotype includes a high frequency of high birth weight, relative macrocephaly, left ventricular hypertrophy, and ectodermal findings, such as curly hair, hyperpigmentation, and wrinkled palms and soles. Short stature and pectus deformity were less frequent. The majority of patients with a RIT1 mutation did not show apparent intellectual disability. Because of the relatively high frequency of mutations in RIT1 among patients with NS and its occurrence in different populations, we suggest that it should be added to the list of genes included in panels for the molecular diagnosis of NS through targeted next-generation sequencing. (c) 2014 Wiley Periodicals, Inc. (AU) | |
| FAPESP's process: | 11/17299-3 - Clinical and molecular study of patients with Noonan and Noonan-like syndromes: phenotypic characterization and searching for new mutations |
| Grantee: | Débora Romeo Bertola |
| Support Opportunities: | Regular Research Grants |