KIF11 microdeletion is associated with microcephaly, chorioretinopathy and intellectual disability

Area of Science:

• Genetics
• Developmental Biology
• Ophthalmology

Background:

• Mutations in the KIF11 gene are linked to autosomal dominant microcephaly-lymphedema-chorioretinopathy dysplasia syndrome.
• This syndrome can be associated with varying degrees of intellectual disability.
• The precise mechanisms of KIF11-related disorders are still being elucidated.

Purpose of the Study:

• To investigate the genetic basis of microcephaly, chorioretinopathy, and mild intellectual disability in a familial cohort.
• To determine if microdeletions encompassing the KIF11 gene contribute to this phenotype.

Main Methods:

• Clinical evaluation of a father and two children presenting with specific developmental and ophthalmological features.
• Molecular genetic analysis, including chromosomal microarray to detect microdeletions.
• Analysis of the KIF11 gene region within the identified microdeletion.

Main Results:

• A 209-kb microdeletion at chromosomal locus 10q23.33 was identified in all affected individuals.
• This microdeletion completely encompasses the KIF11 gene.
• The identified phenotype in this family includes microcephaly, chorioretinopathy, and mild intellectual disability.

Conclusions:

• KIF11 haploinsufficiency resulting from deletions is a causative factor for autosomal dominant microcephaly, chorioretinopathy, and mild intellectual disability.
• This study highlights deletions as a mechanism for KIF11 haploinsufficiency, in addition to point mutations.
• The findings broaden the spectrum of KIF11-related genetic disorders.