The reference OMIM entry for this protein is 600224

Spinocerebellar ataxia 5; sca5

A number sign (#) is used with this entry because of evidence that spinocerebellar ataxia-5 (SCA5) is caused by heterozygous mutation in the SPTBN2 (604985) on chromosome 11q13. Homozygous mutation in the SPTBN2 gene causes autosomal recessive spinocerebellar ataxia-14 (SCAR14; 615386).

DESCRIPTION

For a general discussion of autosomal dominant spinocerebellar ataxia (SCA), see SCA1 (164400).

CLINICAL FEATURES

Ranum et al. (1994) examined a large kindred in which 56 of 170 individuals distributed over 10 generations were affected by a dominant ataxia that was clinically and genetically distinct from those previously mapped. The family had 2 major branches, both of which descended from the paternal grandparents of President Abraham Lincoln. Disease onset varied from 10 to 68 years and anticipation was evident. There were several 3-generation examples of grandmothers having onsets 10 to 20 years later in life than their daughters, who in turn had onsets 10 to 20 years later in life than their children. Furthermore, all 4 cases of juvenile onset (10 to 18 years) were instances of maternal inheritance. Stevanin et al. (1999) reported a French family with SCA5. The overall clinical phenotype was a slowly progressive cerebellar syndrome beginning in the third decade (range, 14 to 40 years). Burk et al. (2004) reported a large German family in which 15 members spanning 4 generations were affected with SCA in an autosomal dominant pattern of inheritance. Mean age at onset was 32.8 years (range, 15 to 50 years), with a tendency toward earlier onset in later generations. The most consistent clinical feature was downbeat nystagmus; 3 affected patients had downbeat nystagmus as an isolated feature. Other common features included gait, stance, and limb ataxia, dysarthria, intention tremor, resting tremor, impaired smooth pursuit, and gaze-evoked nystagmus. Symptom progression was slow, and all patients were ambulatory despite disease duration of up to 31 years. MRI showed atrophy of the cerebellar vermis and hemispheres. - Clinical Variability Jacob et al. (2012) reported a 12-year-old girl with congenital onset of SCA5. She presented in early infancy with hypotonia and global developmental delay, and began walking with a wide-based gait at age 3 to 4 years. Other features included intention tremor, mild dysarthria, nystagmus, facial myokymia, dysmetria, dysdiadochokinesis, hyperreflexia, and ankle clonus. Brain imaging showed mildly progressive cerebellar atrophy. She was in a normal school with a modified program and was very social. There was no family history of a neurologic disorder.

MAPPING

By linkage analysis in a large American family with SCA, Ranum et al. (1994) mapped the disease locus, designated SCA5, to the centromeric region of chromosome 11. In a large German family with autosomal dominant SCA, Burk et al. (2004) found linkage to a 6.5-cM (6.35-Mb) interval on chromosome 11q13 (maximum multipoint lod score of 5.76 between markers D11S1883 and D11S4136). In combination with previous linkage data (Koob et al., 1995), Burk et al. (2004) narrowed the SCA5 locus to a 5.15-Mb interval between PYGM (608455) and D11S4136.

MOLECULAR GENETICS

In affected individuals from an 11-generation American kindred descended from President Lincoln's grandparents whose spinocerebellar ataxia mapped to chromosome 11q13, as well as in 2 additional families, Ikeda et al. (2006) found mutations in the SPTBN2 gene (6 ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 600224 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).