Expanding the Clinical Phenotype Associated with the NIN Gene; Report of a Patient with Short Stature, Microcephaly and Hearing Loss

TL;DR

This paper reports a new case of a patient with a NIN gene variant, linking it to a rare condition with short stature, microcephaly, and hearing loss.

Contribution

The study expands the known clinical features of NIN gene variants to include hearing loss in microcephalic primordial dwarfism.

Findings

A patient with a NIN gene variant showed microcephaly, short stature, and intellectual disability.

The patient also had bilateral hearing loss, a previously unreported symptom in NIN-related disorders.

The variant p.Glu1136del is predicted to disrupt centrosome-related pathways.

Abstract

To date, there are very few reports regarding patients with bi-allelic variants in the NIN gene. There is one report of two sisters with severe short stature, microcephaly, and developmental delay with compound heterozygote missense variants in the NIN gene and one paper reporting a homozygote variant in the NIN gene with progressive, high-frequency sensorineural hearing loss in four siblings. The only other report is of four members of a consanguineous family with spondyloepimetaphyseal dysplasia with joint laxity-leptodactylic type (SEMDJL2) with a homozygous variant in the NIN gene. Given the scarcity of cases with NIN variants, the relationship between the phenotype and gene is provisional and our case broadens the phenotypic spectrum regarding the phenotype related to NIN gene variants. Here, we report a patient with a homozygous variant in exon 2 of the NIN gene defined as c.3407_3409del (p.Glu1136del). Clinical findings in our patient were characteristic of microcephalic primordial dwarfism (MPD) including microcephaly, prominent nose, intellectual disability and severe short stature. In addition, this patient had bilateral hearing loss, which was not reported in the patients with MPD and variant in the NIN gene before. We identified a novel p.Glu1136del variant in the NIN gene, predicted to disrupt critical centrosome-related pathways. WES was reanalyzed for other genes which are known for deafness and no variant was identified. A family history of deafness was not present in the pedigree. This is the first report of a patient with MPD and deafness associated with the NIN gene.

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