Letter to the Editor
A novel AFG3L2 mutation in a Somalian patient with spinocerebellar ataxia type 28

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Introduction

Spinocerebellar ataxias (SCA) are a genetically heterogeneous, autosomal dominant group of neurological disorders consisting of slowly progressive gait and limb ataxia, imbalance, and dysarthria. Of the SCA subtypes identified, spinocerebellar ataxia type 28 (SCA28) is one of 11 subtypes not caused by repeat expansions [1]. SCA28 is due to heterozygous missense mutations in the ATPase family gene 3-like 2 (AFG3L2) gene with at least 13 mutations to date [2], [3], [4]. AFG3L2 is located on chromosome 18p11.22-q11.2, contains 17 exons, and codes for a subunit of m-AAA protease located on the inner mitochondrial membrane [2], [3], [4], [5], [6]. Recent genetic findings also include cases of a frameshift mutation, a heterozygous deletion, and a partial deletion of the AFG3L2 gene.

Although more prevalent in early adulthood, age of onset for SCA28 may vary from 3 to 60. A recent study, however, has identified a frameshift mutation causing late-onset SCA28 at age 68 [7]. SCA28 symptoms primarily include slowly progressive gait and limb ataxia, dysarthria, and nystagmus. Ptosis, opthalmoparesis, and hyperreflexia of the lower limbs can also occur. To date, current literature has only reported cases in Caucasian populations. We present a new AFG3L2 mutation (G > A transition at 571, codon V191I) of SCA28 in the first known case of a patient of African descent and late age of onset.

Section snippets

Genetic analysis

A complete genetic ataxia panel was performed by Athena Diagnostics (Worcester, MA). Abnormal sequence variants were confirmed with bidirectional sequencing of the PCR gene fragments (Please refer to the Athena website for further details).

Case report

A 78 year old Somalian male experienced progressively worsening balance problems beginning in 2005. In 2011, he presented after development of an orthostatic tremor while standing, which restricted his ability to stand from a kneeling position during daily

Discussion

Most SCA28 mutations occur in exons 15 and 16 of the M41-protease domain of the mitochondrial m-AAA metalloprotease complex [4]. The mutation leads to cytotoxicity from reactive oxygen species, thereby inhibiting oxidative phosphorylation in the Purkinje fibers. We report the first known case of an African patient with a novel missense (571:G > A) mutation in exon 4 of the AFG3L2 gene. To date, SCA28 has only been found in Caucasian patients, none of whom have the mutation described.

While the

Author contributions

Ms. Qu, Ms. Wu, Dr. Zuzuárregui and Dr. Hohler contributed to drafting and revising the manuscript.

Dr. Hohler was responsible for the study concept.

Disclosures

Ms. Qu reports no disclosures.

Ms. Wu reports no disclosures.

Dr. Zuzuárregui reports no disclosures.

Dr. Hohler reports no disclosures.

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    Spinocerebellar ataxia type 28: a novel autosomal dominant cerebellar ataxia characterized by slow progression and opthalmoparesis

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