Clefting

Gene: SEPT9

I don't know

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

Created: 1 Feb 2023, 5:13 p.m. | Last Modified: 1 Feb 2023, 5:13 p.m.

Panel Version: 3.5

I don't know

Comment on list classification: There is only 1 report of clefting in a patient with a variant in SEPT9 and a diagnosis of HNA. Other reports of clefting are in patients in which the molecular cause of the disease were not established. Therefore, the recommendation is to demote this gene from green to amber following GMS review.

Created: 21 Jul 2021, 6:59 p.m. | Last Modified: 21 Jul 2021, 6:59 p.m.

Panel Version: 2.46

Reports of clefting
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PMID: 11739810 - Jeannet et al 2001 - characterize the clinical, neurologic, and craniofacial features in 27 patients from seven families with HNA. 4 are reported to have cleft palate. No molecular analysis. Abstract only accessed.

PMID: 18492087 - Laccone et al 2008 - 2 siblings with hereditary neuralgic amyotrophy (HNA) were found to have with a heterozygous missense variant in SEPT9 inherited from the affected father. 1 sibling had a cleft palate.

Reports without clefting (but with identification of variants in SEPT9 in patients with HNA)
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PMID: 30019529 - Neubauer et al 2019 - 1 Lebanese family with a heterozygous duplication of exon 2 of SEPT9 in all the affected family members. No clefting reported.
PMID: 31619932 - Serin et al 2019 - 1 family. Missense variant identified in SEPT9. No clefting reported.
PMID: 28503616 - Chuck et al 2016 - 1 family. Missense variant identified in SEPT9. No clefting reported.
PMID: 20019224 - Ueda et al 2010 - 6 members of a Japanese family with a missense variant in SEPT9. No clefting reported.
PMID: 19939853 - Collie et al 2010 - report 6 additional HNA pedigrees containing duplications within the SEPT9 gene. Clinical presentation was of classical HNA. No further details given.
PMID: 19451530 - Hannibal et al 2009 - report 8 pedigrees with 2 different missense mutations in SEPT9 in HNA patients. Phenotype information not given.
PMID: 19139049 - Landsverk et al 2009 - report 12 North American families that share the common founder haplotype and an intragenic 38 Kb SEPT9 duplication that is linked to HNA. Phenotype information not given.
PMID: 16186812 - Kuhlenbäumer et al 2005 - report 6 families with a variant in SEPT9 and HNA. 3 different variants. In 5 families dysmorphic features are noted but no further information given.

Created: 21 Jul 2021, 6:56 p.m. | Last Modified: 21 Jul 2021, 6:56 p.m.

Panel Version: 2.44

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

• 11739810
• 18492087
• 30019529
• 31619932
• 28503616
• 20019224
• 19939853
• 19451530
• 19139049
• 16186812

I don't know

I can only find one report from 2008 of dysmorphic features including cleft palate co-occurring with HNA.

Created: 13 May 2021, 8:21 p.m. | Last Modified: 13 May 2021, 8:21 p.m.

Panel Version: 2.28

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Amyotrophy, hereditary neuralgic, MIM# 162100

Publications

• 18492087

Added new-gene-name tag, new approved HGNC gene symbol for SEPT9 is SEPTIN9

Created: 7 May 2019, 11:54 a.m.

Green List (high evidence)

Clefting is a reported feature (4 or 27 in one review). Sufficient cases

Created: 26 May 2017, 7:40 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
AMYOTROPHY, HEREDITARY NEURALGIC; HNA