Novel KIAA1109 gene mutation in surviving patients with
Alkuraya-Kučinskas syndrome and a review of literature
Abstract
Alkuraya-Kučinskas syndrome is an autosomal recessive disorder
characterized by brain abnormalities associated with cerebral
parenchymal underdevelopment, arthrogryposis, club foot and global
developmental delay. Mutations in KIAA1109, a functionally
uncharacterized gene causes Alkuraya-Kučinskas syndrome. Most of these
mutations result in premature termination of pregnancies or neonatal
deaths in addition to few surviving patients with global developmental
delay and intellectual disability. Up until recently, only three
surviving patients from two families have been reported with missense
variants in KIAA1109. Here, we describe four additional surviving
patients from two related families (a multiplex family) with global
developmental delay and mild to severe intellectual disability, with no
other systemic manifestations. There were no miscarriages or neonatal
deaths reported in these families. Whole exome sequencing revealed a
homozygous missense mutation in a highly conserved region of KIAA1109
protein. Sanger sequencing confirms the segregation of the mutation in
both the families in autosomal recessive fashion. Our study is the
second study reporting a KIAA1109 variant in surviving patients with
Alkuraya-Kučinskas syndrome. Our study expands the spectrum of clinical
phenotypic features and mutations associated with Alkuraya-Kučinskas
syndrome.