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Genotype-phenotype correlations in Noonan syndrome


Zenker, Martin; Buheitel, Gernot; Rauch, Ralf; Koenig, Rainer; Bosse, Kirstin; Kress, Wolfram; Tietze, Hans-Ulrich; Doerr, Helmuth-Guenther; Hofbeck, Michael; Singer, Helmut; Reis, André; Rauch, Anita (2004). Genotype-phenotype correlations in Noonan syndrome. Journal of Pediatrics, 144(3):368-74.

Abstract

OBJECTIVE

To study genotype-phenotype correlations in a cohort of clinically well-characterized pediatric patients with Noonan syndrome (NS). Study design Fifty-seven unrelated patients with the clinical diagnosis of NS ascertained according to standardized inclusion criteria were prospectively enrolled. Mutational analysis was performed by direct sequencing of the entire coding sequence of the PTPN11 gene.

RESULTS

Sixteen known and 3 novel PTPN11 mutations could be detected in 60% of index patients, in all familial and in 52% of the sporadic cases. Presence of pulmonic stenosis, short stature, easy bruising, and thorax deformities was significantly associated with a PTPN11 mutation, whereas cardiomyopathy was more common in patients without a mutation. On average, PTPN11 mutation-negative probands fulfilled fewer clinical criteria of NS, but more than half-among them all with cardiomyopathy-had the full clinical picture of NS indistinguishable from typical cases with PTPN11 mutation.

CONCLUSIONS

The phenotype of NS due to PTPN11 mutations is clinically unambiguous in the majority of patients and represents a highly penetrant trait. Individuals with the clinical diagnosis of NS but without a PTPN11 mutation presumably represent a heterogeneous group in which patients with cardiomyopathy appear to constitute an interesting subgroup for future research.

Abstract

OBJECTIVE

To study genotype-phenotype correlations in a cohort of clinically well-characterized pediatric patients with Noonan syndrome (NS). Study design Fifty-seven unrelated patients with the clinical diagnosis of NS ascertained according to standardized inclusion criteria were prospectively enrolled. Mutational analysis was performed by direct sequencing of the entire coding sequence of the PTPN11 gene.

RESULTS

Sixteen known and 3 novel PTPN11 mutations could be detected in 60% of index patients, in all familial and in 52% of the sporadic cases. Presence of pulmonic stenosis, short stature, easy bruising, and thorax deformities was significantly associated with a PTPN11 mutation, whereas cardiomyopathy was more common in patients without a mutation. On average, PTPN11 mutation-negative probands fulfilled fewer clinical criteria of NS, but more than half-among them all with cardiomyopathy-had the full clinical picture of NS indistinguishable from typical cases with PTPN11 mutation.

CONCLUSIONS

The phenotype of NS due to PTPN11 mutations is clinically unambiguous in the majority of patients and represents a highly penetrant trait. Individuals with the clinical diagnosis of NS but without a PTPN11 mutation presumably represent a heterogeneous group in which patients with cardiomyopathy appear to constitute an interesting subgroup for future research.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Genetics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Pediatrics, Perinatology and Child Health
Language:English
Date:March 2004
Deposited On:09 Jun 2021 08:56
Last Modified:25 Apr 2024 01:37
Publisher:Elsevier
ISSN:0022-3476
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.jpeds.2003.11.032
PubMed ID:15001945