Klinik Araştırma

The Impact of Paternal Age on RASopathies: Insights from a Clinical Case Series

Cilt: 36 Sayı: 2026 4 Mart 2026
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The Impact of Paternal Age on RASopathies: Insights from a Clinical Case Series

Öz

Aim: RASopathies are a group of genetic disorders caused by germline mutations in genes involved in the RAS/MAPK signaling pathway. These syndromes, including Noonan, Costello, and cardiofaciocutaneous (CFC syndromes, are typically inherited in an autosomal dominant manner but often occur sporadically due to de novo mutations. To reassess our single-center case series with clearer framing of the paternal age effect (PAE), strengthen interpretability with explicit terminology, expanded limitations, and pragmatic clinical implications. Methods: We retrospectively reviewed 25 clinically and molecularly confirmed RASopathy cases diagnosed at Ümraniye Training and Research Hospital (2018-2022). Six patients with inherited variants were excluded, leaving 19 cases with de novo variants for analysis. For each proband, we documented the causal gene/variant, inheritance, and paternal age at conception. Analyses are descriptive; no control cohort was available. Results: Mutations were most frequently identified in SOS1 (36.8%) and PTPN11 (26.3%). All 19 patients harbored de novo mutations, and two mutations (in RAF1 and NF1) were classified as novel. Paternal ages ranged from 25 to 43 years, with a mean of 34.0 years and a median of 33 years. Nine fathers (47.4%) were aged ≥35 years, consistent with the commonly accepted threshold for advanced paternal age. Conclusion: This series is consistent with a paternal age effect in RAS/MAPK–activating disorders. Given the modest sample and lack of controls, causal inference is limited. We outline practical counseling points and a prospective design to validate PAE magnitude in our setting.

Anahtar Kelimeler

RASopathies, Paternal Age Effect, De Novo Mutations. Genetic Counseling

Etik Beyan

This retrospective study was conducted using anonymized data obtained from archived records. According to institutional and national guidelines, ethics committee approval was not required. The study was carried out in accordance with the principles of the Declaration of Helsinki.

Teşekkür

We are grateful to all the patients and their families, whose clinical data made this study possible.

Kaynakça

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Kaynak Göster

APA
Kendir Demirkol, Y., & Yeter, B. (2026). The Impact of Paternal Age on RASopathies: Insights from a Clinical Case Series. Genel Tıp Dergisi, 36(2026), 1-4. https://doi.org/10.54005/geneltip.1771492
AMA
1.Kendir Demirkol Y, Yeter B. The Impact of Paternal Age on RASopathies: Insights from a Clinical Case Series. Genel Tıp Derg. 2026;36(2026):1-4. doi:10.54005/geneltip.1771492
Chicago
Kendir Demirkol, Yasemin, ve Burcu Yeter. 2026. “The Impact of Paternal Age on RASopathies: Insights from a Clinical Case Series”. Genel Tıp Dergisi 36 (2026): 1-4. https://doi.org/10.54005/geneltip.1771492.
EndNote
Kendir Demirkol Y, Yeter B (01 Mart 2026) The Impact of Paternal Age on RASopathies: Insights from a Clinical Case Series. Genel Tıp Dergisi 36 2026 1–4.
IEEE
[1]Y. Kendir Demirkol ve B. Yeter, “The Impact of Paternal Age on RASopathies: Insights from a Clinical Case Series”, Genel Tıp Derg, c. 36, sy 2026, ss. 1–4, Mar. 2026, doi: 10.54005/geneltip.1771492.
ISNAD
Kendir Demirkol, Yasemin - Yeter, Burcu. “The Impact of Paternal Age on RASopathies: Insights from a Clinical Case Series”. Genel Tıp Dergisi 36/2026 (01 Mart 2026): 1-4. https://doi.org/10.54005/geneltip.1771492.
JAMA
1.Kendir Demirkol Y, Yeter B. The Impact of Paternal Age on RASopathies: Insights from a Clinical Case Series. Genel Tıp Derg. 2026;36:1–4.
MLA
Kendir Demirkol, Yasemin, ve Burcu Yeter. “The Impact of Paternal Age on RASopathies: Insights from a Clinical Case Series”. Genel Tıp Dergisi, c. 36, sy 2026, Mart 2026, ss. 1-4, doi:10.54005/geneltip.1771492.
Vancouver
1.Yasemin Kendir Demirkol, Burcu Yeter. The Impact of Paternal Age on RASopathies: Insights from a Clinical Case Series. Genel Tıp Derg. 01 Mart 2026;36(2026):1-4. doi:10.54005/geneltip.1771492