Novel frameshift duplication mutation in the ACER۳ gene in patient with Leukodystrophy: Case report

Introduction: Leukodystrophies are genetic disease of myelin manufacture affecting the central nervous system. The frequency of these diseases is estimated at about ۱ in ۷۶۶ births. ACER۳ (Alkaline Ceramidase ۳) is a Coding gene. Diseases associated with ACER۳ include Leukodystrophy, Progressive, and Early Childhood-Onset. The mainsymptoms of neurologic features included truncal hypotonia, appendicular spasticity, dystonia, areflexia, pale optic discs, and neurogenic bladder. Case presentation: This study presents a ۴-years-old boy with developmental delay, intellectual disability, muscle weakness in lower limb, muscular dystrophy, renal tubular acidosis (RTA). His MRI scan revealed cerebral atrophy and periventricular leukomalacia(PVL). Based on clinical/para-clinical investigations the referring physician suggested Cerebral palsy or/and Metachromatic leukodystrophy as a possible diagnosis for him. His parents are first cousins. Finally, a whole-exome sequencing test was done for the patient. The results showed a novel homozygous duplication mutation (c.۵۰۵_۵۰۶dupCC) in exon ۸ of the ACER۳ gene. Although this mutation has not been reported yet for Leukodystrophy, Progressive, and Early Childhood-Onset, the frequency of it in normal population is low. After this observation, we perform the Sanger sequencing for his parents. As a result, his parents showed a heterozygous mutation in the same gene and same location. Conclusions: Homozygosity for the W۱۷۰Hfs*۲۳ mutation in the ACER۳ gene results in the inactivation of ACER۳ that can lead to the accumulation of various sphingolipids in blood and probably in the brain, likely accounting for this new form of childhood leukodystrophy. This data can be used in early diagnosis of future generations and effective genetic counseling in this family.

کلیدواژه ها:

ACER۳ ، Frameshift Duplication ، Leukodystrophy.