Ataxia and cerebellar anomalies - narrow panel

Gene: SAR1B

Red List (low evidence)

The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.

Created: 5 Feb 2023, 5:18 p.m. | Last Modified: 5 Feb 2023, 5:18 p.m.

Panel Version: 3.30

Comment on list classification: Leaving rating as green, but with recommendation of a red rating following GMS review. Ataxia rarely reported and as the expert reviewer notes this is secondary to malabsorption.

Created: 30 Jun 2021, 4:44 p.m. | Last Modified: 30 Jun 2021, 4:44 p.m.

Panel Version: 2.215

Associated only with Chylomicron retention disease #246700 in OMIM.

PMID: 12692552 - Jones et al 2003 - report 8 families with homozygous/compound het variants in SAR1B. The affected individuals had a diagnosis of Chylomicron retention disease (CMRD), Anderson disease or CMRD with the neuromuscular disorder Marinesco–Sjogren syndrome (CMRD-MSS) all of which are inherited disorders of severe fat malabsorption. The patient described in this paper had no ataxia reported. PMID: 3792776, 7601203 (abstract only), 2426307 and 10521380, describe some of the patients and ataxia is not reported. However, the 2 Italian siblings whose phenotype is described in PMID: 10665502 with a Marinesco-Sjogren syndrome diagnosis showed severe cerebellar ataxia with truncal and limb ataxia, Very low Vit E concentrations were noted.

PMID: 17945526 - Charcosset et al 2008 - report 15 new cases of chylomicron retention disease among 8 families from France and Canada. Patients were referred for symptoms of malabsorption syndrome (diarrhea, steatorrhea and failure to thrive). They note that all patients had very low levels of fat soluble vitamin E, but neurological and ophtalmological abnormalities were rarely observed at onset of the disease among them.

Created: 30 Jun 2021, 4:42 p.m. | Last Modified: 30 Jun 2021, 4:42 p.m.

Panel Version: 2.214

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Chylomicron retention disease, OMIM:246700

Publications

• 12692552
• 3792776
• 7601203
• 2426307
• 10521380
• 10665502
• 17945526

Red List (low evidence)

Ataxia is not a reported prominent feature of the condition. Neurological symptoms are secondary to malabsorption.

Created: 12 Sep 2020, 7:45 a.m. | Last Modified: 12 Sep 2020, 7:45 a.m.

Panel Version: 2.12

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Chylomicron retention disease, 246700