Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation

Kouz, Karim; Lißewski, Christina; Spranger, Stephanie; Mitter, Diana; Rieß, Angelika; López‐González, Vanesa; Lüttgen, Sabine; Aydın, Hatip; Deimling, Florian von; Evers, Christina; Hahn, Andreas; Hempel, Maja; Issa, Ulrike; Kahlert, Anne‐Karin; Lieb, Adrian; Villavicencio‐Lorini, Pablo; Ballesta-Martínez, María Juliana; Nampoothiri, Sheela; Ovens-Raeder, Angela; Puchmajerová, Alena; Satanovskij, Robin; Seidel, Heide; Unkelbach, Stephan; Zabel, Bernhard; Kutsche, Kerstin; Zenker, Martin

doi:10.1038/gim.2016.32

Cited by 78 publications

(98 citation statements)

References 40 publications

(84 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Four novel missense pathogenic variants in the RIT1 gene were detected in our study and evaluated as disease‐related variants. Recent research showed that short stature (31%), intellectual problems (27%), and pectus anomalies (42%) were less frequent in RIT1 group patients but there was a high prevalence of HCM (42%) and lymphatic problems . Similar results were observed in this study.…”

Section: Discussionsupporting

confidence: 89%

Molecular and phenotypic spectrum of Noonan syndrome in Chinese patients

Yao

Tan

et al. 2019

Clinical Genetics

View full text Add to dashboard Cite

Noonan syndrome (NS) is a common autosomal dominant/recessive disorder. No large‐scale study has been conducted on NS in China, which is the most populous country in the world. Next‐generation sequencing (NGS) was used to identify pathogenic variants in patients that exhibited NS‐related phenotypes. We assessed the facial features and clinical manifestations of patients with pathogenic or likely pathogenic variants in the RAS‐MAPK signaling pathway. Gene‐related Chinese NS facial features were described using artificial intelligence (AI).NGS identified pathogenic variants in 103 Chinese patients in eight NS‐related genes: PTPN11 (48.5%), SOS1 (12.6%), SHOC2 (11.7%), KRAS (9.71%), RAF1 (7.77%), RIT1 (6.8%), CBL (0.97%), NRAS (0.97%), and LZTR1 (0.97%). Gene‐related facial representations showed that each gene was associated with different facial details. Eight novel pathogenic variants were detected and clinical features because of specific genetic variants were reported, including hearing loss, cancer risk due to a PTPN11 pathogenic variant, and ubiquitous abnormal intracranial structure due to SHOC2 pathogenic variants. NGS facilitates the diagnosis of NS, especially for patients with mild/moderate and atypical symptoms. Our study describes the genotypic and phenotypic spectra of NS in China, providing new insights into distinctive clinical features due to specific pathogenic variants.

show abstract

Section: Discussionsupporting

confidence: 89%

Molecular and phenotypic spectrum of Noonan syndrome in Chinese patients

Yao

Tan

et al. 2019

Clinical Genetics

View full text Add to dashboard Cite

show abstract

“…According to the Developmental Disorders Genotype-Phenotype Database, the genes LMNA , NTRK1, and RIT1 are confirmed as causing developmental disorders in multiple unrelated cases [Indo et al, 1997;Aoki et al, 2013;Kouz et al, 2016]. There is currently no literature to support a haploinsufficient effect of RIT1 .…”

Section: Discussionmentioning

confidence: 99%

A de novo 1q22q23.1 Interstitial Microdeletion in a Girl with Intellectual Disability and Multiple Congenital Anomalies Including Congenital Heart Defect

Aleksiūnienė

Preikšaitienė²,

Morkūnienė³

et al. 2018

Cytogenet Genome Res

View full text Add to dashboard Cite

Many studies have shown that molecular karyotyping is an effective diagnostic tool in individuals with developmental delay/intellectual disability. We report on a de novo interstitial 1q22q23.1 microdeletion, 1.6 Mb in size, detected in a patient with short stature, microcephaly, hypoplastic corpus callosum, cleft palate, minor facial anomalies, congenital heart defect, camptodactyly of the 4-5th fingers, and intellectual disability. Chromosomal microarray analysis revealed a 1.6-Mb deletion in the 1q22q23.1 region, arr[GRCh37] 1q22q23.1(155630752_157193893)×1. Real-time PCR analysis confirmed its de novo origin. The deleted region encompasses 50 protein-coding genes, including the morbid genes APOA1BP, ARHGEF2, LAMTOR2, LMNA, NTRK1, PRCC, RIT1, SEMA4A, and YY1AP1. Although the unique phenotype observed in our patient can arise from the haploinsufficiency of the dosage-sensitive LMNA gene, the dosage imbalance of other genes implicated in the rearrangement could also contribute to the phenotype. Further studies are required for the delineation of the phenotype associated with this rare chromosomal alteration and elucidation of the critical genes for manifestation of the specific clinical features.

show abstract

“…phenotype of pulmonary valve stenosis rather than cardiac hypertrophy, there are at least 9 additional NS-susceptibility genes, including SOS1 (7,8), RAF1 (9,10), KRAS (11), RIT1 (12,13), NRAS (14), RRAS (15), CBL (16), and SOS2 and LZTR1 (17). A mutation in SHOC2 is responsible for NS-like disorder with loose anagen hair (NS-LAH; MIM 607721) (18).…”

Section: Introductionmentioning

confidence: 99%