A Novel Mutation (c.122T>A) of PEX11B Gene in a Female Adolescent with Congenital Cataract and Clubfoot

Author(s): Vasiliki Rengina Tsinopoulou*, Liana Fidani, Styliani Giza, Eleni I Sakellari, Angeliki Beslika, Stergianna Ntouma, Spyridon Gerou, Assimina Galli-Tsinopoulou

Objective: Peroxisome biogenesis disorder type 14B (PEX14B, OMIM #614920) is an autosomal recessive disorder characterized clinically by mild mental retardation, congenital cataract, progressive hearing loss, and polyneuropathy. We aimed to report a new mutation in a female adolescent of Greek origin with prominent clinical signs of congenital cataract and clubfoot.

Material: A 134/12-year-old girl having overweight, mild psychomotor retardation, congenital cataract, clubfoot from infancy progressively worsening with accompanying unsteadiness of gait, episodes of faecal incontinence in the dolichosigmoid setting and non-autoimmune hypothyroidism was presented. On clinical examination, furrows, lowered eyelid fissures and corners of the mouth, a deep philtrum and micrognathia were noted and neurologically found reduced muscle strength in the peripheral parts of the upper and lower limbs with absence of tendon reflexes and atrophy of the thenar, peroneal and tibial muscles both, findings indicative of peripheral polyneuropathy, which was confirmed in the neurophysiological examination. Neuroimaging, metabolic control and karyotype reveled normal findings. Whole Exome Sequencing (WES) was performed.

Results: The unreported nucleotide substitution c122T>A in the PEX11B gene was found in the homozygous state, causing premature termination of protein synthesis and impaired biogenesis of type 14B peroxisomes. Heterozygosity for the same mutation was found in parents.

Conclusions: DNA sequencing of all genes is an excellent tool for the diagnosis of phenotypically and genetically heterogeneous conditions such as as disorders of hyperhyxosome biogenesis. The detection of new mutations helps to complete the clinical and genetic spectrum of rare diseases and constitutes a valuable learning resource for future research.