<i>ILDR1</i> reported mutations, described effects and predicted consequences using insilico analysis.

<p><i>ILDR1</i> reported mutations, described effects and predicted consequences using insilico analysis.</p

Identification of a novel frameshift mutation in the <i>ILDR1</i> gene in a UAE family, mutations review and phenotype genotype correlation

<div><p>Autosomal recessive non-syndromic hearing loss is one of the most common monogenic diseases. It is characterized by high allelic and locus heterogeneities that make a precise diagnosis difficult. In this study, whole-exome sequencing was performed for an affected patient allowing us to identify a new frameshift mutation (c.804delG) in the Immunoglobulin-Like Domain containing Receptor-1 (<i>ILDR1)</i> gene. Direct Sanger sequencing and segregation analysis were performed for the family pedigree. The mutation was homozygous in all affected siblings but heterozygous in the normal consanguineous parents. The present study reports a first <i>ILDR1</i> gene mutation in the UAE population and confirms that the whole-exome sequencing approach is a robust tool for the diagnosis of monogenic diseases with high levels of allelic and locus heterogeneity. In addition, by reviewing all reported <i>ILDR1</i> mutations, we attempt to establish a genotype phenotype correlation to explain the phenotypic variability observed at low frequencies.</p></div

Electropherograms.

<p>Homozygous normal individual (A), Heterozygous individual (B), and affected individual with the c.804delG pathogenic variant in the <i>ILDR1</i> gene (NM_001199799.1) (C).</p

Pedigree of the affected family, Audiogram and PCR-RFLP analysis.

<p>(A) Pedigree of the affected family with nonsyndromic hearing loss. Arrow denotes the proband. (B) Audiogram of the proband individual II-1 exhibiting bilateral, severe to profound sensorineural hearing loss. (C) Results of PCR-RFLP analysis of DNA of the affected family with nonsyndromic hearing loss. A 993 bp PCR fragment is digested with FauI restriction enzyme. The wildtype DNA is cleaved into four fragments 538, 222, 136 and 97 bp, whereas the c.804delG mutant allele is cleaved into three fragments 635, 222 and 136 bp in length. MW: DNA Ladder (100bp DNA Ladder, REF G2101) (Promega, USA); ND: undigested PCR product.</p

In silico analysis and predicted effect at the protein level of c.3G>A, c.59-5_88del and c.499+1G>A mutations.

<p>In silico analysis and predicted effect at the protein level of c.3G>A, c.59-5_88del and c.499+1G>A mutations.</p