Spinocerebellar ataxia 28 (SCA28) is typically caused by autosomal dominant mutations in the AFG3L2 gene. However, Pierson TM et al (2011) have reported a family in which a homozygous hypomorphic allele (c.1847A>Gp.Y616C) is segregating as homozygous in affected patients. This form of AFG3L2-related SCA is called SCAX5 (see OMIM 614487). Hypomorphic alleles are consistent with mutations which can worsen the phenotype of some autosomal dominantly inherited genetic diseases. Examples of hypomorphic alleles have been reported in PKD1-related polycystic kidneys. However, homozygosity for hypomorphic alleles is not regularly reported as cause of disease. So this AFG3L2 mutation seems to be quite an exception.
References: see text.
