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A novel PAX2 heterozygous mutation in a family with Papillorenal syndrome: A case report and review of the literature.

ABSTRACT:

Purpose

Papillorenal syndrome (PAPRS) is a rare inherited disorder often involves abnormalities of eye and kidney. Paired box 2 (PAX2) gene, which is widely expressed in the development of the organs including kidney, ureter, eye, ear, and central nervous system has been considered an underlying cause of PAPRS. The present work aims to further our understanding of PAX2 gene and PAPRS by reporting a family with PAPRS associated with a novel PAX2 mutation and describing ocular manifestation of PAX2 mutation in previous literatures.

Observation

We herein present a family with PAPRS presented with typical congenital optic disc defects and mild renal dysplasia. Through screening of candidate genes based on the next-generation sequencing, the heterozygous PAX2 mutation c.175C > T (p. Arg59Trp) was identified which had never been reported.

Conclusions

The study expands the genetic and clinic spectrum of PAPRS. Further review of detailed ocular manifestation and genotypes of PAX2 mutation in previous study improves the recognition of the ocular phenotypes' spectrum, assists in the identification of PAPRS. Moreover, this study reveals that PAPRS is a systemic disorder with heterogeneous diverse phenotypes, and shows the importance of gene panel sequencing in the diagnosis of PAPRS which could achieve high diagnostic rates.

SUBMITTER: Liu S

PROVIDER: S-EPMC8102412 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveNoonan syndrome (NS), an autosomal dominant disease known as a RASopathy, is caused by germline mutations in mitogen-activated protein kinase pathway genes. A RIT1 gene mutation has been found to cause NS. The present study summarizes RIT1 gene mutation sites and associated clinical phenotypes.MethodsWe retrospectively analyzed the clinical characteristics of a case of NS caused by RIT1 mutation in our hospital, and searched the PubMed database, China National Knowledge Infrastructure (CNKI) database and Wanfang database with the keywords Noonan syndrome and RIT1. Studies published between May 1, 2014 and July 1, 2021 were retrieved. By reviewing the abstracts and full text of the studies, we screened NS cases associated with RIT1 mutation in children 0-18 years of age. The clinical characteristics of these cases were summarized.ResultsA total of 41 cases were analyzed, including 13 boys and 28 girls. There were 14 premature cases. The age at diagnosis was 4 days to 18 years, and 10 cases were diagnosed at 0-1 years of age. Common amino acid substitution positions included 57 (13/41), 95 (7/41), 82 (8/41), and 90 (4/41). A total of 63.63% cases had abnormal prenatal examination results, manifesting mainly as fetal neck edema, polyhydramnios and cardiac malformation. With respect to abnormal conditions after birth, 70-80% of patients had typical developmental malformations of the face, neck and thorax; 19/35 patients had abnormal lymphatic development; and a portion of patients had short stature and motor development disorders. A total of 87.80% (36/41) patients had cardiac dysplasia, among which hypertrophic cardiomyopathy (HCM) accounted for 58.53%. A total of 84.62% of patients carrying the p.A57G mutation had HCM, but no HCM was found in patients with the p.G95A mutation. A total of 34.15% of patients had pulmonary artery or pulmonary valve stenosis (PVS). In patients with the p.M90I mutation, 75% had PVS. Patients with concurrent HCM and PVS accounted for 19.51 and 48.78% of patients had supraventricular tachycardia.ConclusionA RIT1 gene mutation causing NS was associated with a high rate of abnormal prenatal examination findings. Most patients had typical NS craniofacial deformities, and some have short stature and motor development disorders. The cardiac deformity rate was high, and HCM was common. Some patients had supraventricular arrhythmias. Heart abnormalities showed high heterogeneity, given the various mutation loci.