Dataset Information

A Chinese family with Noonan syndrome caused by a heterozygous variant in LZTR1: a case report and literature review.

ABSTRACT:

Background

Noonan syndrome is an inherited disease involving multiple systems. More than 15 related genes have been discovered, among which LZTR1 was discovered recently. However, the pathogenesis and inheritance pattern of LZTR1 in Noonan syndrome have not yet been elucidated.

Case presentation

We herein describe a family with LZTR1-related Noonan syndrome. In our study, the proband, sister, mother, maternal aunt and grandmother and female cousin showed the typical or atypical features of Noonan syndrome. Only 3 patients underwent the whole-exome sequencing analysis and results showed that the proband as well as her sister inherited the same heterozygous LZTR1 variant (c.1149?+?1G?>?T) from their affected mother. Moreover, the proband accompanied by growth hormone deficiency without other associated variants.

Conclusion

In a Chinese family with Noonan syndrome, we find that the c.1149?+?1G?>?T variant in LZTR1 gene shows a different autosomal dominant inheritance from previous reports, which changes our understanding of its inheritance and improves our understanding of Noonan syndrome.

SUBMITTER: Zhao X

PROVIDER: S-EPMC7788825 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Chinese family with Noonan syndrome caused by a heterozygous variant in LZTR1: a case report and literature review.

Zhao Xiu X Li Zhuoguang Z Wang Li L Lan Zhangzhang Z Lin Feifei F Zhang Wenyong W Su Zhe Z

BMC endocrine disorders 20210106 1

<h4>Background</h4>Noonan syndrome is an inherited disease involving multiple systems. More than 15 related genes have been discovered, among which LZTR1 was discovered recently. However, the pathogenesis and inheritance pattern of LZTR1 in Noonan syndrome have not yet been elucidated.<h4>Case presentation</h4>We herein describe a family with LZTR1-related Noonan syndrome. In our study, the proband, sister, mother, maternal aunt and grandmother and female cousin showed the typical or atypical fe ...[more]

PMID: 33407364

Similar Datasets

Project description:ObjectiveNoonan syndrome (NS), an autosomal dominant disease known as a RASopathy, is caused by germline mutations in mitogen-activated protein kinase pathway genes. A RIT1 gene mutation has been found to cause NS. The present study summarizes RIT1 gene mutation sites and associated clinical phenotypes.MethodsWe retrospectively analyzed the clinical characteristics of a case of NS caused by RIT1 mutation in our hospital, and searched the PubMed database, China National Knowledge Infrastructure (CNKI) database and Wanfang database with the keywords Noonan syndrome and RIT1. Studies published between May 1, 2014 and July 1, 2021 were retrieved. By reviewing the abstracts and full text of the studies, we screened NS cases associated with RIT1 mutation in children 0-18 years of age. The clinical characteristics of these cases were summarized.ResultsA total of 41 cases were analyzed, including 13 boys and 28 girls. There were 14 premature cases. The age at diagnosis was 4 days to 18 years, and 10 cases were diagnosed at 0-1 years of age. Common amino acid substitution positions included 57 (13/41), 95 (7/41), 82 (8/41), and 90 (4/41). A total of 63.63% cases had abnormal prenatal examination results, manifesting mainly as fetal neck edema, polyhydramnios and cardiac malformation. With respect to abnormal conditions after birth, 70-80% of patients had typical developmental malformations of the face, neck and thorax; 19/35 patients had abnormal lymphatic development; and a portion of patients had short stature and motor development disorders. A total of 87.80% (36/41) patients had cardiac dysplasia, among which hypertrophic cardiomyopathy (HCM) accounted for 58.53%. A total of 84.62% of patients carrying the p.A57G mutation had HCM, but no HCM was found in patients with the p.G95A mutation. A total of 34.15% of patients had pulmonary artery or pulmonary valve stenosis (PVS). In patients with the p.M90I mutation, 75% had PVS. Patients with concurrent HCM and PVS accounted for 19.51 and 48.78% of patients had supraventricular tachycardia.ConclusionA RIT1 gene mutation causing NS was associated with a high rate of abnormal prenatal examination findings. Most patients had typical NS craniofacial deformities, and some have short stature and motor development disorders. The cardiac deformity rate was high, and HCM was common. Some patients had supraventricular arrhythmias. Heart abnormalities showed high heterogeneity, given the various mutation loci.

Project description:BackgroundMarfan syndrome (MFS) is a common autosomal dominant inherited disease, and the occurrence rate is around 0.1-0.2‰. The causative variant of FNB1 gene accounts for approximately 70-80% of all MFS cases. In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene. This finding extended the variant spectrum of the FBN1 gene and will provide a solution for patients to bear healthy offspring by preimplantation genetic testing or prenatal diagnosis.Case presentationThe patient was treated due to tachycardia during excitement in a hospital. Echocardiography showed dilatation of the ascending aorta and main pulmonary artery, mitral regurgitation (mild), tricuspid regurgitation (mild), and abnormal left ventricular filling. Electrocardiograph showed sinus rhythm. In addition, flutters of shadows in front of his eyes and vitreous opacity were present in the patient. Genomic DNA was extracted from peripheral blood samples from members of the family and 100 unrelated controls. Potential variants were screened out by next-generation sequencing and confirmed by MLPA & Sanger sequencing. Real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect the relative mRNA quantitation in the patient. A heterozygous nonsense variant c.3217G > T of the FBN1 gene, which resulted in p. Glu1073Term, was identified in both patients. Only wild type bases were found in the cDNA sequence of the patient. Real-time fluorogenic quantitative PCR results showed that the relative expression level of FBN1 cDNA in the patient was only about 21% compared to that of normal individuals. This variant c.3217G > T of the FBN1 gene introduces a Stop codon in the cb-EGF12 domain. We speculated that a premature translational-termination codon (PTC) was located in the mRNA and the target mRNA was disintegrated through a process known as nonsense-mediated mRNA decay (NMD), which led to a significant decrease of the fibrillin-1 protein, eventually causing clinical symptoms in the patient.ConclusionsIn this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene, which eventually led to Marfan syndrome in a Chinese family.

Project description:BackgroundPrimary ciliary dyskinesia (PCD) is a type of ciliary dyskinesia that is usually caused by autosomal recessive inheritance and can manifest as recurrent respiratory infections, bronchiectasis, infertility, laterality defects, and chronic otolaryngological disease. Although ependymal cilia, which affect the flow of cerebrospinal fluid in the central nervous system, have much in common with respiratory cilia in terms of structure and function, hydrocephalus is rarely associated with PCD. Recently, variants of Forkhead box J1 (FOXJ1) have been found to cause PCD combined with hydrocephalus in a de novo, autosomal dominant inheritance pattern.MethodsWe performed DNA extraction, whole-exome sequencing (WES) analysis, and mutation analysis of FOXJ1 and analyzed the patient's clinical and genetic data.ResultsThe patient was a 4-year-old female exhibiting normal growth and development. At 3 years and 2 months of age, the patient experienced hand shaking and weakness in the lower limbs. Cardiac ultrasonography showed a right-sided heart, and cranial magnetic resonance imaging showed obstructive hydrocephalus. The nasal nitric oxide level was 54 nL/min. WES indicated a de novo, heterozygous variant of FOXJ1, c.734-735 ins20. This variant was novel, not included in the Human Gene Mutation and Genome Aggregation Database, and likely pathogenic according to the American College of Medical Genetics and Genomics, causing earlier termination of amino acid translation. The patient underwent a neuroendoscopic third ventriculostomy after the diagnosis of obstructive hydrocephalus. Six months after the operation, the patient's motor deficits had improved.ConclusionThis is the first report of a de novo, autosomal dominant pattern of FOXJ1 causing PCD combined with hydrocephalus in China. The patient's clinical symptoms were similar to those previously reported. WES confirmed that a novel variant of FOXJ1 was the cause of the PCD combined with hydrocephalus, expanding the spectrum of the genotypes associated with this condition. Physicians should be aware of the correlation of hydrocephalus and PCD and test for FOXJ1 variants.

Dataset Information

A Chinese family with Noonan syndrome caused by a heterozygous variant in LZTR1: a case report and literature review.

Background

Case presentation

Conclusion

Publications

A Chinese family with Noonan syndrome caused by a heterozygous variant in LZTR1: a case report and literature review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets