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| Paediatric disorders - additional genes v8.11 | SEC31A | Ida Ertmanska Classified gene: SEC31A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v8.11 | SEC31A | Ida Ertmanska Added comment: Comment on list classification: There are now 3 unrelated probands reported with 3 unique homozygous variants in SEC31A and a highly syndromic presentation, resulting in early lethality. A neuron-specific sec31a knock-down in Drosophila recapitulated early lethality seen in the patients. Based on available evidence, this gene should be Green on Paediatric disorders - additional genes. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v8.11 | SEC31A | Ida Ertmanska Gene: sec31a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v8.10 | SEC31A |
Ida Ertmanska gene: SEC31A was added gene: SEC31A was added to Paediatric disorders - additional genes. Sources: Literature Q3_26_promote_green tags were added to gene: SEC31A. Mode of inheritance for gene: SEC31A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SEC31A were set to 30464055; 39725565; 40508110 Phenotypes for gene: SEC31A were set to ?Halperin-Birk syndrome, OMIM:618651; neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, MONDO:0032849 Review for gene: SEC31A was set to GREEN Added comment: PMID: 39725565 Almontashiri et al., 2025 Female proband; parents are first cousins. IUGR and multiple congenital anomalies were seen on the antenatal scan. She was born very small, with dysmorphic facial features. She had hypotonia with hyperreflexia, but no seizures. Head ultrasound revealed absent CC and an interhemispheric cyst. She had short bowed limbs, contractures, Wormian skull bones, shortening of the long bones, and microcephaly. She died at 15 days old due to bradycardia. Solo WES revealed a homozygous SEC31A splice variant c.1435-1G>A. Splice AI score is Splice-Altering / strong (1) for this variant. RT-PCR showed exon skipping and overall reduction in SEC31A expression. PMID: 40508110 AlTassan et al., 2025 Report of a 5yo male proband with global developmental delay, seizure disorder, hypotonia, spasticity, dysphagia, dysmorphic features, and bilateral hearing loss. Growth parameters indicated microcephaly, failure to thrive, and short stature. He was born to consanguineous parents. WES and WGS showed a homozygous SEC31A variant (c.1359C>G, p.Cys453Trp) - variant not in gnomAD v4.1.1. Unaffected parents confirmed het. Parents confirmed to be consanguineous, Arab ethnicity. PMID: 30464055 Halperin et al., 2018 2 Bedouin sibs from a consanguineous family. The syndromic presenation included IUGR, marked developmental delay, spastic quadriplegia with profound contractures, pseudobulbar palsy with recurrent aspirations, epilepsy, dysmorphism, neurosensory deafness, optic nerve atrophy with no eye fixation, bilateral cataracts, microcephaly, and agenesis of CC. Focal and generalised tonic-clonic seizures were seen from birth. Both individuals died before age 4 years. Seq method: homozygosity mapping, WES. Both affected individuals were homozygous for the SEC31A: c.2776_2777dup, p.Ala927Thrfs*76 variant - not in gnomAD v4.1.1. Functional evidence: Drosophila sec31a -/- null model showed early embryonic lethality. Knockdown of sec31a with RNAi in the eye yielded flies with severe eye phenotypes (disorganised ommatids). Brain-specific knockdown: larvae appeared to develop normally until death in the third instar larvae stage. Sources: Literature |
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