PhD Scientific Days 2021

CL_V_P: Clinical Medicine V. Posters

Co-occurrence of Two Autosomal Dominant Disorders Revealed by Genetic Testing

Text of the abstract

Introduction
Neurofibromatosis type 1 (NF1) is an autosomal dominant disease caused by mutation in the NF1 gene. It is a neurocutaneous disorder occurring approximately in 1:3000 individuals, characterised by several dermatologic, neurologic, and ophthalmologic manifestations.
Pseudoachondroplasia (PSACH) is caused by mutation in the COMP gene inherited also in an autosomal dominant manner. The disease is part of the bone dysplasia family affecting approximately 1:20,000 individuals.
Aims
Here we report the case of a young girl presenting with several skeletal and dermatologic anomalies. Our aims were to reveal the underlying genetic characteristics causing this unique phenotype.
Method
Written informed consent was obtained from all individual participants. DNA was isolated from peripheral leukocytes. Conventional PCR amplification and bidirectional Sanger sequencing of the exonic regions of NF1 and COMP genes was performed on the DNA sample of the index patient and both available family members.
Results
An 8-year-old female and her parents presented to Genetic Counselling. The index patient had rhizomelic stature, café-au-lait macules, freckling in the axillary and inguinal region, genu varum, knee hypermobility, waddling gait, and lumbar lordosis. The mother presented with clinical characteristics that met the diagnostic criteria for NF1. The father presented with a phenotype of PSACH, he had disproportionate short stature, short limbs, and several skeletal anomalies. Sequencing of the NF1 gene detected a previously unreported heterozygous, likely pathogenic variant c.1479_1480delCTinsG (p.Leu494CysfsTer3) in the index patient and in her mother. Sequencing of the COMP gene revealed a previously reported, pathogenic heterozygous variant c.1319G>A (p.Gly440Glu) in the index patient and her father.
Conclusions
We reported a patient who inherited two rare autosomal dominant diseases. We believe that this case is the first description of the unique coexistence of neurofibromatosis type 1 and pseudoachondroplasia.
Funding
This work was supported by grants from the National Research, Development and Innovation Office of Hungary– NKFIH (FK_131916, 2019), EFOP-3.6.3-VEKOP-16-2017-00009, and the ÚNKP-20-3-I-SE-24 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund.

University and Doctoral School

Semmelweis University, Károly Rácz Doctoral School of Clinical Medicine