Congenital diaphragmatic hernia as a part of Nance–Horan syndrome?

Kammoun, Molka; Brady, Paul; Catte, Luc De; Deprest, Jan; Devriendt, Koenraad; Vermeesch, Joris Robert

doi:10.1038/s41431-017-0032-z

Cited by 7 publications

(6 citation statements)

References 40 publications

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“…Two novel hemizygous frameshift mutations were identified in NHS , the gene responsible for X-linked Nance Horan syndrome (NHS) [23, 24]: c.3207_3208del; p. (Ala1070Phefs * 16) and c.2739del; p.(Phe913Leufs * 9), in sporadic cases #7 and #8, respectively (Fig. 5c).…”

Section: Resultsmentioning

confidence: 99%

Clinical and genetic characteristics of Chinese patients with familial or sporadic pediatric cataract

Leng

Han

et al. 2018

Orphanet J Rare Dis

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BackgroundPediatric cataract is a clinically and genetically heterogeneous disease which is a significant cause of lifelong visual impairment and treatable blindness. Our study aims to investigate the genotype spectrum in a group of Chinese patients with pediatric cataract.MethodsWe enrolled 39 families with pediatric cataract from October 2015 to April 2016. DNA samples of the probands were analyzed by target next-generation sequencing. Variants were validated using Sanger sequencing in the probands and available family members.ResultsIn our cohort of 39 cases with different types of pediatric cataract, 23 cases were found to harbor putative pathogenic variants in 15 genes: CRYAA, CRYBA1, CRYBA4, CRYBB1, CRYGC, CRYGD, MIP, GCNT2, IARS2, NHS, BCOR, BFSP2, FYCO1, MAF, and PAX6. The mutation detection rates in the familial and sporadic cases were 75 and 47.8%, respectively. Of the 23 causative variants, over half were novel.ConclusionsThis is a rare report of systematic mutation screening analysis of pediatric cataract in a comparably large cohort of Chinese patients. Our observations enrich the mutation spectrum of pediatric cataract. Next-generation sequencing provides significant diagnostic information for pediatric cataract cases, especially when considering sporadic and subtle syndromal cases.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0828-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Clinical and genetic characteristics of Chinese patients with familial or sporadic pediatric cataract

Leng

Han

et al. 2018

Orphanet J Rare Dis

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“…NHS is caused by a mutation in the NHS gene on chromosome Xp22. NHS is usually fully expressed in males only, with the affected males characterized by congenital cataracts and frequent microcornea, dental anomalies, and dysmorphic features [1, 2]. Approximately 20 to 30% of affected males may have varying levels of mental retardation [3].…”

Section: Introductionmentioning

confidence: 99%

Whole exome sequencing identified a novel truncation mutation in the NHS gene associated with Nance-Horan syndrome

et al. 2019

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BackgroundNance-Horan syndrome (NHS) is an X-linked inheritance disorder characterized by bilateral congenital cataracts, and facial and dental dysmorphism. This disorder is caused by mutations in the NHS gene. However, NHS may be difficult to detect in individuals with subtle facial dysmorphism and dental abnormalities in whom congenital cataracts are the primary clinical manifestations.MethodsIn this study, we present a three-generation family with NHS. Whole exome sequencing was performed to determine the potential pathogenic variant in the proband. Further validation was explored with Sanger sequencing in 9 of the available individuals of the family and additional 200 controls.ResultsA novel truncation mutation in gene NHS (c.C4449G, p.Tyr1483Ter) was found in the proband, who presented with a long-narrow face, prominent nose and large anteverted pinnae ear, screw-driver like incisors, mild mulberry like molars, one missing maxillary second molar and malocclusion. We found this mutation was detected in 2 male patients and 4 female carriers in the family. However, the mutation was never detected in the control subjects.ConclusionsIn conclusion, we identified a novel truncation mutation in the NHS gene, which might associate with NHS. Our review on the NHS studies illustrated that NHS has significantly clinical heterogeneity. And NHS mutations in the NHS-affected individuals typically result in premature truncation of the protein. And the new mutation revealed in this study would highlight the understanding of the causative mutations of NHS.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0725-3) contains supplementary material, which is available to authorized users.

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“…Similarly, Pereira-Terra and colleagues described a specific micro-RNA signature in tracheal aspirate fluid, upregulation of miR-200b and miR-10a and decreased TGFB signaling (47). Patients with mutations in genes (64,65). These occurrences of direct genotype-phenotype correlations stress the importance of genetic diagnostic screening to inform parents and patients about possible co-morbidities.…”

Section: Genetic Associations and Co-morbiditymentioning

confidence: 97%

“…Patients with variants in STRA6 and RARB -receptors and deletions of RBP1 at chromosome 3q22 ( 60 , 61 ) in the retinoic acid signaling pathway have ophthalmic symptoms ( 62 , 63 ). Patients with CDH may have other eye defects as well ( 64 , 65 ). These occurrences of direct genotype-phenotype correlations stress the importance of genetic diagnostic screening to inform parents and patients about possible co-morbidities.…”

Section: Genetic Associations and Co-morbiditymentioning

confidence: 99%

Unraveling the Genetics of Congenital Diaphragmatic Hernia: An Ongoing Challenge

et al. 2022

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Congenital diaphragmatic hernia (CDH) is a congenital structural anomaly in which the diaphragm has not developed properly. It may occur either as an isolated anomaly or with additional anomalies. It is thought to be a multifactorial disease in which genetic factors could either substantially contribute to or directly result in the developmental defect. Patients with aneuploidies, pathogenic variants or de novo Copy Number Variations (CNVs) impacting specific genes and loci develop CDH typically in the form of a monogenetic syndrome. These patients often have other associated anatomical malformations. In patients without a known monogenetic syndrome, an increased genetic burden of de novo coding variants contributes to disease development. In early years, genetic evaluation was based on karyotyping and SNP-array. Today, genomes are commonly analyzed with next generation sequencing (NGS) based approaches. While more potential pathogenic variants are being detected, analysis of the data presents a bottleneck—largely due to the lack of full appreciation of the functional consequence and/or relevance of the detected variant. The exact heritability of CDH is still unknown. Damaging de novo alterations are associated with the more severe and complex phenotypes and worse clinical outcome. Phenotypic, genetic—and likely mechanistic—variability hampers individualpatient diagnosis, short and long-term morbidity prediction and subsequent care strategies. Detailed phenotyping, clinical follow-up at regular intervals and detailed registries are needed to find associations between long-term morbidity, genetic alterations, and clinical parameters. Since CDH is a relatively rare disorder with only a few recurrent changes large cohorts of patients are needed to identify genetic associations. Retrospective whole genome sequencing of historical patient cohorts using will yield valuable data from which today's patients and parents will profit Trio whole genome sequencing has an excellent potential for future re-analysis and data-sharing increasing the chance to provide a genetic diagnosis and predict clinical prognosis. In this review, we explore the pitfalls and challenges in the analysis and interpretation of genetic information, present what is currently known and what still needs further study, and propose strategies to reap the benefits of genetic screening.

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Congenital diaphragmatic hernia as a part of Nance–Horan syndrome?

Cited by 7 publications

References 40 publications

Clinical and genetic characteristics of Chinese patients with familial or sporadic pediatric cataract

Clinical and genetic characteristics of Chinese patients with familial or sporadic pediatric cataract

Whole exome sequencing identified a novel truncation mutation in the NHS gene associated with Nance-Horan syndrome

Unraveling the Genetics of Congenital Diaphragmatic Hernia: An Ongoing Challenge

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