A Chinese child with hyperpigmentation diagnosed with familial glucocorticoid deficiency type 1 using whole-exome sequencing

Abstract Background NF1(Neurofibromatosis type 1) is an autosomal dominant genetic disorder. Patients with NF1 have an increased risk of developing benign or malignant tumours, such as gastrointestinal stromal tumours (GISTs). However, the coexistence of NF1, GIST and colon cancer is very rare, and few cases have been reported in the literature. Case presentation We admitted a case of a 64-year-old man with type 1 neurofibromatosis, GISTs, and ascending colon cancer. This case was characterized by café-au-lait macules, discrete cutaneous neurofibromas, nodular neurofibromas, multiple jejunal tumours, and ascending colon cancer. Laparoscopic exploration revealed ascending colon cancer and multiple jejunal tumours. Laparoscopic right hemicolectomy and local excision of the jejunal tumours were performed successfully. The pathological results confirmed moderate differentiated adenocarcinoma of the ascending colon with multiple jejunal GISTs (low risk, very low risk). Moreover, the immunohistochemistry results of multiple jejunal GISTs suggest that NF1 is positive. Whole-exome sequencing (WES) of colon cancer revealed mutations in more than 20 genes, including KRAS, PIK3CA, APC, SMAD4, etc. The results of whole-exome sequencing (WES) of jejunal GISTs revealed an NF1 mutation and no KIT or PDGFR gene mutation. Conclusion We report a rare case of simultaneous NF1, GIST and colon adenocarcinoma. For patients with NF1, benign and/or malignant tumours are often combined. Therefore, these patients should undergo regular physical examinations so that early detection and early treatment can be achieved.

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Novel Mutation C.7348C>T in NF1 Gene Identified by Whole-Exome Sequencing in Patient with Overlapping Clinical Symptoms of Neurofibromatosis Type 1 and Bannayan–Riley–Ruvalcaba Syndrome

Cytology and Genetics ◽

10.3103/s0095452720040106 ◽

2020 ◽

Vol 54 (4) ◽

pp. 353-362

Author(s):

Edris Sharif Rahmani ◽

Hasan Azarpara ◽

Mohammad Foad Abazari ◽

Mohammad Reza Mohajeri ◽

Maryam Nasimi ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Neurofibromatosis Type 1 ◽

Clinical Symptoms ◽

Novel Mutation ◽

Neurofibromatosis Type ◽

Whole Exome ◽

Nf1 Gene

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Correction: Whole Exome Sequencing of Growing and Non-Growing Cutaneous Neurofibromas from a Single Patient with Neurofibromatosis Type 1

PLoS ONE ◽

10.1371/journal.pone.0172620 ◽

2017 ◽

Vol 12 (2) ◽

pp. e0172620

Author(s):

Daniel L. Faden ◽

Saurabh Asthana ◽

Tarik Tihan ◽

Joseph DeRisi ◽

Michel Kliot

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Single Patient ◽

Whole Exome ◽

Cutaneous Neurofibromas

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Whole-Exome Sequencing as a Diagnostic Tool in a Family With Episodic Ataxia Type 1

Mayo Clinic Proceedings ◽

10.1016/j.mayocp.2015.01.001 ◽

2015 ◽

Vol 90 (3) ◽

pp. 366-371 ◽

Cited By ~ 9

Author(s):

Pawel Tacik ◽

Kimberly J. Guthrie ◽

Audrey J. Strongosky ◽

Daniel F. Broderick ◽

Douglas L. Riegert-Johnson ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Diagnostic Tool ◽

Episodic Ataxia ◽

Whole Exome ◽

Episodic Ataxia Type

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Identification of NF1 Frameshift Variants in Two Chinese Families With Neurofibromatosis Type 1 and Early-Onset Hypertension

Frontiers in Pediatrics ◽

10.3389/fped.2021.785982 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yi-Ting Lu ◽

Di Zhang ◽

Xin-Chang Liu ◽

Qiong-Yu Zhang ◽

Xue-Qi Dong ◽

...

Keyword(s):

Blood Pressure ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Neurofibromatosis Type 1 ◽

Early Onset ◽

Family Members ◽

Neurofibromatosis Type ◽

Chinese Families ◽

Whole Exome

Background: Neurofibromatosis type 1 (NF-1) is a common autosomal dominant disorder caused by mutations in the NF1 gene. It is characterized by multiple café-au-lait macules, cutaneous neurofibromas, optic glioma, Lisch nodules, and axillary and inguinal freckling. The aim of this study was to investigate NF1 mutations in two Chinese families with NF-1 who presented with early-onset hypertension, and to determine the prevalence of hypertension associated with NF-1 to better understand this complication.Methods: Whole-exome sequencing was performed for the probands with NF-1 from two unrelated families. Possible pathogenic mutation was predicted by bioinformatic tools. Sanger sequencing was used to confirm candidate variants in all available individuals for familial co-segregation analysis. We also performed a systematic literature review of studies that reported the prevalence of hypertension in patients with NF-1.Results: In family 1, a recurrent mutation c.6789_6792delTTAC in NF1 was identified in the proband but in no other family members, indicating that this is a de novo mutation. In family 2, a novel mutation c.6934_6936delGCAinsTGCT in NF1 was detected in the proband and two other family members, which co-segregated with the disease phenotype within the family. Both mutations were predicted to be pathogenic by bioinformatic analysis. We found hypertension was a relatively common complication of NF-1, with a prevalence range of 6.1–23.4%. Ambulatory blood pressure monitoring is a stable method for detecting initial alterations of the blood pressure pattern, particularly for pre-hypertension.Conclusions: We identified one recurrent (c.6789_6792delTTAC) and one novel frame-shift mutation (c.6934_6936delGCAinsTGCT) in two unrelated families with NF-1 using whole-exome sequencing. In consideration of phenotypic heterogeneity in NF-1, genetic testing is a robust tool which helps early and accurate diagnosis. Because hypertension is not a rare complication of NF-1, routine screening for hypertension in patients with NF-1, especially children and adolescents, is important to avoid serious cardiovascular events.

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