Dataset Information

Next-generation sequencing identifies a novel frameshift variant in FRMD7 in a Chinese family with idiopathic infantile nystagmus.

ABSTRACT: BACKGROUND:Idiopathic infantile nystagmus (IIN) is a high genetically heterogeneous ophthalmic disease and is often associated with pathogenic mutations in FRMD7 and GPR143, respectively. Idiopathic infantile nystagmus manifests as involuntary periodic rhythmic oscillation of the eyes in the very early life, which decreases visual acuity and affects the quality of life. OBJECTIVE AND METHODS:The aim of our study was to reveal a possible pathogenic variant through the investigation of a Chinese Han family with IIN with an implementation of a next-generation sequencing method. Isolated DNA analysis was followed by Sanger sequencing validation. We also performed the detailed ophthalmological examination of family members. RESULTS:We identified a novel frameshift variant in FRMD7 (NM_194277.2: c.1419_1422dup, p.Tyr475fs), which leads to a frameshift mutation since tyrosine (Tyr) at 475 codon of FRMD7 protein (p.Tyr475fs) and co-segregates with IIN phenotype in this family. CONCLUSIONS:We found a novel frameshift FRMD7 variant in a Chinese Han family, which may be causative variant for IIN and can further enrich the mutation spectrum and uncover the etiology of IIN.

SUBMITTER: Wang F

PROVIDER: S-EPMC6977136 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Next-generation sequencing identifies a novel frameshift variant in FRMD7 in a Chinese family with idiopathic infantile nystagmus.

Wang Fengqi F Guan Hongzai H Liu Wenmiao W Zhao Guiqiu G Liu Shiguo S

Journal of clinical laboratory analysis 20190908 1

<h4>Background</h4>Idiopathic infantile nystagmus (IIN) is a high genetically heterogeneous ophthalmic disease and is often associated with pathogenic mutations in FRMD7 and GPR143, respectively. Idiopathic infantile nystagmus manifests as involuntary periodic rhythmic oscillation of the eyes in the very early life, which decreases visual acuity and affects the quality of life.<h4>Objective and methods</h4>The aim of our study was to reveal a possible pathogenic variant through the investigation ...[more]

PMID: 31495972

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Project description:ImportanceInfantile nystagmus syndrome (INS) is a group of disorders presenting with genetic and clinical heterogeneities that have challenged the genetic and clinical diagnoses of INS. Precise molecular diagnosis in early infancy may result in more accurate genetic counseling and improved patient management.ObjectiveTo assess the accuracy of genomic data from next-generation sequencing (NGS) and phenotypic data to enhance the definitive diagnosis of INS.Design, setting, and participantsA single-center retrospective case series was conducted in 48 unrelated, consecutive patients with INS, with or without associated ocular or systemic conditions, who underwent genetic testing between June 1, 2015, and January 31, 2017. Next-generation sequencing analysis was performed using a target panel that included 113 genes associated with INS (n = 47) or a TruSight One sequencing panel that included 4813 genes associated with known human phenotypes (n = 1). Variants were filtered and prioritized by in-depth clinical review, and finally classified according to the American College of Medical Genetics and Genomics guidelines. Patients underwent a detailed ophthalmic examination, including electroretinography and optical coherence tomography, if feasible.Main outcomes and measuresDiagnostic yield of targeted NGS testing.ResultsAmong the 48 patients (21 female and 27 male; mean [SD] age at genetic testing, 9.2 [10.3] years), 8 had a family history of nystagmus and 40 were simplex. All patients were of a single ethnicity (Korean). Genetic variants that were highly likely to be causative were identified in 28 of the 48 patients, corresponding to a molecular diagnostic yield of 58.3% (95% CI, 44.4%-72.2%). FRMD7, GPR143, and PAX6 mutations appeared to be the major genetic causes of familial INS. A total of 10 patients (21%) were reclassified to a different diagnosis based on results of NGS testing, enabling accurate clinical management.Conclusions and relevanceThese findings suggest that NGS is an accurate diagnostic tool to differentiate causes of INS because diagnostic tests, such as electroretinography and optical coherence tomography, are not easily applicable in young infants. Accurate application of NGS using a standardized, stepwise, team-based approach in early childhood not only facilitated early molecular diagnosis but also led to improved personalized management in patients with INS.

Dataset Information

Next-generation sequencing identifies a novel frameshift variant in FRMD7 in a Chinese family with idiopathic infantile nystagmus.

Publications

Next-generation sequencing identifies a novel frameshift variant in FRMD7 in a Chinese family with idiopathic infantile nystagmus.

Similar Datasets

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