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

To date, there are very few reports regarding patients with bi-allelic variants in the gene. There is one report of two sisters with severe short stature, microcephaly, and developmental delay with compound heterozygote missense variants in the gene and one paper reporting a homozygote variant in the 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 gene. Given the scarcity of cases with variants, the relationship between the phenotype and gene is provisional and our case broadens the phenotypic spectrum regarding the phenotype related to gene variants. Here, we report a patient with a homozygous variant in exon 2 of the 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 gene before. We identified a novel p.Glu1136del variant in the 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 gene.