Genotype-phenotype data from a case series of patients with mosaic neurofibromatosis type 1

Marwaha, Ashish; Malach, Jessica; Shugar, Andrea; Hedges, Stephanie; Weinstein, Miriam; Parkin, Patricia C.; Pope, Elena; Lara‐Corrales, Irene; Kannu, Peter

doi:10.1111/bjd.16929

Cited by 9 publications

(10 citation statements)

References 8 publications

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“…In our study nine family has a somatic mosaicism. In such cases the confirmation of the NF1 gene mutation can only be done by molecular analysis of the affected tissues (21)(22)(23)(24). However, in our study, no mutation was studied from the somatic DNA sample in the parents of the children who were found to have mutations, showed clinical findings and did not have a germline NF1 mutation.…”

Section: Discussionmentioning

confidence: 88%

Clinical findings and mutational spectrum of neurofibromatosis type 1 patients in a single center of south part of Turkey

Gündoğan¹,

Bozdoğan²,

Ayhan³

et al. 2021

Turk J Med Sci

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Aim:The aim of this study is to determine the mutation spectrums and clinical characteristics of NF1 patients followed up in our center and to investigate whether there is a genotype-phenotype relationship.Material and Methods: Sixty-three children and 34 relatives diagnosed with NF1 were included in the study. Age, gender, family history, clinical features, tumors detected in the patient at the time of diagnosis or during follow-up, orbital and cerebral magnetic resonance imaging (MRI) findings were recorded. Also results of the NF1 gene analysis results were recorded.Results: Fifty-three different mutations were found as a result of the NF1 gene analysis studied from patients and their family members. Among these 53 mutations, stop codon mutation was the most frequently detected mutations. Sixteen out of 50 (32%) mutations were found to be novel mutations. Twenty-eight tumors developed in our patients. Twenty of them were optic gliomas and others were medullary thyroid carcinoma, glioblastome multiforme, pons glioma, acute lymphoblastic leukemia, pilocytic astrositoma, hypothalamic glioma, cerebral hamartoma and cardiac fibroma.No genotype-phenotype relationship was detected in patients Conclusion: Comprehensive mutation analysis of NF1 will increase our knowledge due to its different phenotypic characteristics even in the same mutation.

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Section: Discussionmentioning

confidence: 88%

Clinical findings and mutational spectrum of neurofibromatosis type 1 patients in a single center of south part of Turkey

Gündoğan¹,

Bozdoğan²,

Ayhan³

et al. 2021

Turk J Med Sci

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“…Our patient is cognitively normal and had noticed the development of neurofibromas while in his late thirties. He also had Lisch nodules, which were not frequently observed regardless of the patient's age in other cohorts 3 , 6 , 12 . He is currently on annual follow-up for his cutaneous presentations.…”

Section: Discussionmentioning

confidence: 90%

“…The eighth patient had cafe-au-lait macules, a plexiform neurofibroma and sphenoid wing dysplasia but no freckling. Only one patient had Lisch nodules 12 .…”

Section: Discussionmentioning

confidence: 97%

Case Report: Mosaicism of a novel nonsense variant in the neurofibromin gene underlies a mosaic generalized NF1 phenotype

2021

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Neurofibromatosis 1 (NF1) is a neurocutaneous syndrome characterized by multiple café-au-lait macules, cutaneous neurofibromas or plexiform neurofibromas, iris Lisch nodules, axillary and inguinal freckling. Mosaicism in NF1 can either present as a generalized disease, or in a localized (segmental) manner. Mosaic generalized NF1 may have presentations that are similar to generalized NF1 or have a milder phenotype and hence may be under-recognised in clinical practice. We report a nonsense mutation in the NF1 gene in a 55-year old Chinese male with the mosaic generalized phenotype. He reported noticing increasing numbers of skin-colored papules over his face, neck, back and abdomen when he was about 40 years old. From both next-generation and Sanger sequencing data, the variant appeared to be mosaic and present at about 24%. It is in exon 39 and has not been reported in any database or published literature.

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“…Another case had a daughter with generalized NF1 and two unaffected children consistent with gonadal mosaicism (24). (21,22). In 11 cases a pathogenic NF1 variant was detected; an intragenic variant in nine cases and a microdeletion in two cases (21,22).…”

Section: Clinical Featuresmentioning

confidence: 98%

Clinical Features and Disease Severity in Patients With Mosaic Neurofibromatosis Type 1: A Single-Center Study and Literature Review

Raundahl¹,

Gregersen

Handrup

et al. 2020

Preprint

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Background The mosaic form of neurofibromatosis type 1 (NF1) is called mosaic NF1 (MNF1). No specific MNF1 follow-up guidelines exist. It is debatable if patients with MNF1 should be clinically examined and undergo follow-up in accordance with the standard NF1 guidelines, as MNF1 patients more often may develop more benign phenotypes and thereby less disease-associated complications including cognitive impairment. We discussed the need for a specific MNF1 follow-up guideline with focus on frequency of plexiform neurofibromas and NF1-associated complications.Method A systematic retrospective data collection in a MNF1 cohort from one of two Danish national centers of NF1 Expertise was completed. Data collected included demographics, clinical features including NF1 diagnostic criteria and NF1-associated complications. Recent literature in the field was reviewed.Results We identified 17 patients with MNF1 with a median age of 37 years [4; 66]. Eleven (65%) were females. Five patients (30%) had a plexiform neurofibroma. The median age at detection of plexiform neurofibroma was 30 years [14; 60]. Nine (53%) had at least one NF1-related complication; scoliosis, hypertension, ADHD, learning disability, language delay, autism and delay in gross and fine motor function development. We reviewed nine articles. In total, 126 cases were described within three case-series. Nineteen (15%) had a plexiform neurofibroma and in total, 23 NF1-associated complications were reported including language delay, learning disability and skeletal abnormalities. Furthermore, from the literature it was evident that the diagnosing of MNF1 varies among physicians and across countries. Conclusion Patients with MNF1 present with plexiform neurofibromas and other NF1-related complications with a frequency requiring that follow-up of MNF1 patients should be in accordance with the standard NF1 guideline in both childhood and adulthood. Physicians should be aware of cognitive impairment as a complication to MNF1. To develop a specific MNF1 follow-up guideline, there is a need for an international consensus on the diagnostic criteria for MNF1 and a follow-up study conducted in a larger MNF1 cohort.

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Genotype-phenotype data from a case series of patients with mosaic neurofibromatosis type 1

Cited by 9 publications

References 8 publications

Clinical findings and mutational spectrum of neurofibromatosis type 1 patients in a single center of south part of Turkey

Clinical findings and mutational spectrum of neurofibromatosis type 1 patients in a single center of south part of Turkey

Case Report: Mosaicism of a novel nonsense variant in the neurofibromin gene underlies a mosaic generalized NF1 phenotype

Clinical Features and Disease Severity in Patients With Mosaic Neurofibromatosis Type 1: A Single-Center Study and Literature Review

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