Médecine moléculaire et génétique

An ABCD1 Mutation (c.253dupC) Caused Diverse Phenotypes of Adrenoleukodystrophy in an Iranian Consanguineous Pedigree

Abstract

Masoud Mehrpour, Faeze Gohari, Majid Zaki Dizaji, Ali Ahani, May Christine V. Malicdan and Babak Behnam

Objectives: Current study was the first to report a consanguineous Iranian pedigree with ABCD1 mutation.

Methods: Targeted molecular analysis was initially performed in three affected individuals in one family suspected to have X-ALD due to chronic progressive spasticity. Upon confirmation of genetic diagnosis, further neurologic and genetic evaluation of all family members was done.

Results: A mutation in ABCD1 was identified in 35 affected individuals (out 96 pedigree members). The c. 253dup, in exon 1, leads to a frame shift and a premature stop codon at amino acid position 194 (p.Arg85Profs*110). Surprisingly, affected individuals in our cohort show some variability in phenotype, including childhood cerebral ALD, adrenomyeloneuropathy, and addison-only disease phenotypes, expanding the phenotype of X-ALD with p.Arg85Profs*110.

Conclusion: This report characterizes the clinical spectrum of an expanded Iranian pedigree with X-ALD due to an ABCD1 mutation. Given a high frequency of carriers in this region, we expect the prevalence of X-ALD to be higher, underscoring the importance of genetic counseling through reliable identification of heterozygous as well as homozygote females in consanguineous communities.