Genetic variations in patient with Parry-Romberg syndrome

Abstract

Parry-Romberg syndrome is a rare craniofacial disorder which is characterized by progressive facial atrophy. The etiology and pathogenesis of the disease are not known. Herein, we report the genetic variants in patient with this disease. A 25-year-old woman was diagnosed with Parry-Romberg syndrome according to her clinical manifestation, which presented with typical progressive unilateral facial soft tissue atrophy. Using peripheral blood samples, Whole exome sequencing (WES) was conducted on this patient and her parents. Variant loci of the genes were validated by Sanger sequencing in her twin sister who had no Parry-Romberg syndrome. Subsequently, we searched the GeneCards^®: the Human Gene Database for variant genes, annotated them and analyzed their functions. The results of WES showed that 2 genes (MTOR, DHX37) were mutated, and the variant loci were MTOR: NM_004958.4: exon31: c.4487A>T: p.Q1496L and DHX37: NM_032656.4: exon17: c.2180C>T: p.T727M, respectively. However, the variant loci were also detected in her twin sister by Sanger sequencing. The Human Gene Database for variant genes shows that the two genes may be associated with craniomaxillofacial developmental abnormalities. Although MTOR and DHX37 genes were tested and found to have mutations in patient with Parry-Romberg syndrome, these variants may not directly determine the clinical phenotype. When studying clinical etiology, other factors, such as the environment, should also be taken into account.

Figure 1

Variation characteristics of two gene loci. (A) The genetic map of the patient's family showed that there was only one case of Parry–Romberg syndrome in the patient's family. (B) The Sanger sequencing verification results of the patient's sister showed that the patient's sister also had the same genetic locus mutation.

Figure 2

Photos of the patient's face before and after treatment. (A–C) Preoperative photos of patient. (D) Photo after two operations—autologous fat transplantation on the atrophic face and local flap transfer.

Figure 3

The mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MTOR and DHX37 genes. The results showed high transcript levels of both genes in immune system, skin and skeletal muscle.

Figure 4

The protein expression levels in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MTOR and DHX37 genes. The results showed that the genes have a high level of protein expression in both blood and immune system.

Figure 5

Interacting proteins analysis from STRING Interaction Network. The top 5 and 25 STRING interactants of both MTOR and DHX37 genes are shown in this figure.