A further case of AFG2B‐related neurodevelopmental disorder with hearing loss and microcephaly allows further clarification of pathogenicity of the variant c.1313TC, p.(Leu438Pro)
You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
A further case of AFG2B‐related neurodevelopmental disorder with hearing loss and microcephaly allows further clarification of pathogenicity of the variant c.1313TC, p.(Leu438Pro)
Description:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Bi‐allelic variants in <jats:italic>AFG2B</jats:italic> (previously known as <jats:italic>SPATA5L1</jats:italic>) have recently been associated with a neurodevelopmental disorder with hearing loss and spasticity, as well as isolated hearing loss. We report on a 6 1/2‐year‐old girl with a history of global developmental delay, subsequent intellectual disability without relevant language acquisition, sensorineural hearing loss, muscular hypotonia and microcephaly.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We performed trio exome sequencing on the patient and her parents.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Trio exome sequencing revealed likely pathogenic compound heterozygous missense variants in <jats:italic>AFG2B</jats:italic> [c.527G>T, p.(Gly176Val) and c.1313T>C, p.(Leu438Pro)] in the patient.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Of note, the change c.1313T>C, p.(Leu438Pro) has been observed in a previously published patient as part of a complex disease allele along with a second homozygous missense change, so the exact contribution of the two alterations to this patient's disease had initially remained unclear. Our results support the pathogenic relevance of the c.1313T>C, p.(Leu438Pro) allele while providing detailed insights into the disease manifestation of a further patient.</jats:p></jats:sec>