# Whole-exome sequencing revealed a likely pathogenic variant in NF1 causing neurofibromatosis type I and Arrhythmogenic Cardiomyopathy

## TL;DR

Whole-exome sequencing identified a likely pathogenic variant in the NF1 gene in an Iranian patient with neurofibromatosis type I and arrhythmogenic cardiomyopathy.

## Contribution

A novel likely pathogenic NF1 variant is reported in a patient with both NF1 and ACM, highlighting the role of WES in genetic diagnosis.

## Key findings

- A heterozygous missense variant c.3277G > A:p.Val1093Met in the NF1 gene was identified as likely pathogenic.
- The variant was confirmed by PCR and Sanger sequencing, and no family members showed the same mutation.
- The patient exhibited clinical features consistent with arrhythmogenic cardiomyopathy.

## Abstract

Neurofibromatosis type I (NF1) is a genetic disorder characterized by the tumor’s development in nerve tissue. Complications of NF1 can include pigmented lesions, skin neurofibromas, and heart problems such as cardiomyopathy. In this study, we performed whole-exome sequencing (WES) on an Iranian patient with NF1 to identify the genetic cause of the disease.

Following clinical assessment, WES was used to identify genetic variants in a family with a son suffering from NF1. No symptomatic manifestations were observed in other family members. In the studied family, in silico and segregation analysis were applied to survey candidate variants.

Clinical manifestations were consistent with arrhythmogenic cardiomyopathy (ACM). WES detected a likely pathogenic heterozygous missense variant, c.3277G > A:p.Val1093Met, in the NF1 gene, confirmed by PCR and Sanger sequencing. The patient’s parents and brother had a normal sequence at this locus.

Although there is no cure for NF1, genetic tests, such as WES, can detect at-risk asymptomatic family members. Furthermore, cardiac evaluation could also help these patients before heart disease development.

The online version contains supplementary material available at 10.1186/s12872-024-03878-z.