Early onset or syndromic epilepsy

Gene: KIF1BP

I don't know

previuosly known as KIAA1279. Traditionally, this variant this gene are not associated with seizures per se. Differential diagnosis would include: Loeys-Dietz syndrome (LDS), Marfan syndrome (MFS), and Mowat-Wilson syndrome (MOWS). AR Goldberg-Shprintzen megacolon syndrome (GOSHS). No mention on OMIM that epilepsy is a feature. Brooks et al 2005 - says that patients with GOSHS discussed in published reports - neurological symptoms not studied in detail. Large consang Moroccan family with HSCR reported by Brooks et al, 1999 - hom nonsense variant detected. Also looked at a consang British-Pakistani family - diff hom nonsense variant. No mention that either of these families had epilepsy. Salehpour et al, 2017 - 16 year old Iranian patient GOSHS and refractory seizures - hom nonsense variant detected. They have a table of other reported mutations of which there are 7 all are nonsense or lead to premature stop. No mention in the clinical features of any of these other cases of seizures (table 1).

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Goldberg-Shprintzen megacolon syndrome, 609460

Publications

• 23427148

I don't know

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green, and an Amber rating is appropriate. Demoted from Green to Amber.

Created: 15 Aug 2019, 8:39 a.m. | Last Modified: 15 Aug 2019, 8:39 a.m.

Panel Version: 1.224

Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary: although the association with GOLDBERG-SHPRINTZEN MEGACOLON SYNDROME is strong, there is little direct evidence for seizures (PMID:28277559 identifies one case). Therefore consider demoting KIF1BP.

Created: 15 Aug 2019, 8:39 a.m. | Last Modified: 15 Aug 2019, 10:28 a.m.

Panel Version: 1.236

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

PMID:28277559: Salehpour et al., 2017 report a 16 year old male from Iran with features of Goldberg-Shprintzen syndrome plus refractory seizures. He had a nonsense homozygous variant in KIAA1279/KIF1BP (p.Q326X).

Created: 22 Jul 2019, 12:51 p.m. | Last Modified: 22 Jul 2019, 12:51 p.m.

Panel Version: 1.176

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Goldberg-Shprintzen megacolon syndrome

Publications

• Brooks et al (2005) Am J Hum Genet 77: 120_126

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Goldberg-Shprintzen megacolon syndrome

Publications

• Brooks et al (2005) Am J Hum Genet 77: 120_126

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Goldberg-Shprintzen megacolon syndrome

Publications

• Brooks et al (2005) Am J Hum Genet 77: 120_126

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Goldberg-Shprintzen megacolon syndrome

Publications

• Brooks et al (2005) Am J Hum Genet 77: 120 126

Variants in this GENE are reported as part of current diagnostic practice

Added new-gene-name tag, new approved HGNC gene symbol for KIF1BP is KIFBP

Created: 6 Sep 2019, 2:59 p.m. | Last Modified: 6 Sep 2019, 2:59 p.m.

Panel Version: 1.263

added new-gene-name tag

Created: 9 Dec 2016, 3:22 p.m.

Changed the gene symbol back to KIAA1279 in order to be consistent with PanelApp's HGNC versioning, prior to update.

Created: 8 Dec 2016, 11:26 a.m.

This gene symbol was converted from KIAA1279 to KIF1BP (new HGNC-approved symbol), as confirmed in HGNC, G2P and OMIM databases.

Created: 1 Feb 2016, 9:45 a.m.

The HGNC-approved symbol for this gene is KIF1BP (confirmed on G2P and OMIM).

Created: 20 Jan 2016, 12:53 p.m.

Comment on phenotypes: Phenotype sourced from reviewers, OMIM and G2P.

Created: 20 Jan 2016, 12:52 p.m.