Autosomal Recessive Chorea Acanthocytosis

Rubio et al. performed linkage analysis of 11 families with presumed chorea-acan-thocytosis (ChAc) [17]. A clinical diagnosis of ChAc in each family was based on a neurological syndrome characterized by an abnormal movement disorder, myopa-thy, neuropathy, seizures, neuropsychiatric abnormalities, and the presence of acanthocytosis, and the absence of McLeod syndrome or abetalipoproteinaemia. Two of the families in the linkage study were described in Hardie's series of 1991 (CHAC family 1 and CHAC family 9). In 1997, Rubio et al. reported linkage of the genetic abnormality in these 11 families to a 6-cM region on chromosome 9q21 [17]. The results confirmed that in all 11 cases ChAc was a homogeneous autosomal recessive disorder.

In 2001, Rampoldi and colleagues succeeded in identifying the CHAC gene [14] (now VPS13A). Sixteen distinct mutations were identified in the 11 ChAc families which co-segregated with other affected family members. Of the 11 families, three had homozygous mutations of VPS13A in affected members, six had compound heterozygous mutations in VPS13A and two had a single heterozygous mutation in VPS13A. From the original Hardie series, a compound heterozygous mutation 269T^A (exon 4) and 6404-6405insT (exon 48) was identified in ChAc family 1. A single heterozygous mutation 8162A^G (exon 27) was identified in ChAc family 9. This has raised the question as to whether a second mutation in VPS13A is present and was not detected, or whether a single mutation in VPS13A is sufficient to cause disease in certain cases.

0 0

Post a comment