Genetic and Clinical Phenotypic Analysis of Familial Stapes Sclerosis Caused by a NOG Mutation

Abstract

Background：Noggin protein encoded by NOG gene can interfere with the binding of bone morphogenetic protein to its receptor, thus affecting bone and joint develop pment. The symptoms include abnormal skeletal development and conductive deaf ness Methods: In a Retrospective study, clinical data of the proband and her family members include 8 people and 50 healthy normal controls were collected. Secon d-generation sequencing were performed on peripheral blood samples from them. Results：The sequencing analysis indicated that, in the probrand, the NOG gene included c.532T>C (cytosine deletion), leading to an amino acid change. The prob and's father, grandmother, second sister, and third sister also had this mutation, whereas those with normal phenotypes did not have the mutation. Conclusion：Analysis of this family showed that the new presentation of c.532T>C mutation in the NOG gene resulted in syndrome-type autosomal dominant inheritan ce reflected in a mild clinical phenotype, which is of great significance for further studies of the clinical phenotype and pathogenesis of stapetectopia.

A familial case of NOG-related symphalangism spectrum disorder due to a novel NOG variant

“…In general, no strict correlation between pathological variants and specific phenotypes was found. Several reports underline that the same NOG sequence pathogenic variation can produce different inter or intrafamilial phenotypes, in particular concerning the degree of joint or bone deformities (Hirshoren et al , 2008; Masuda et al , 2014; Ganaha et al , 2015; Ishino et al , 2015; Takano et al , 2016; Shu et al , 2019, Yu et al , 2020). No definite correlation was found between the protein position in different domains and the phenotype, even if it was pointed out that in cases with stapes ankylosis without SYM1 the cysteine-rich C-terminal domain is primarily disrupted (Dixon et al , 2001; Usami et al , 2012; Lee et al , 2014; Ganaha et al , 2015; Ma et al , 2019).…”