Severe microcephalyGene: SASS6
Comment on list classification: Promoting from red to amber as now two cases reported with severe microcephaly. Pubmed search did not find further cases at this time.
Created: 20 May 2021, 10:28 a.m. | Last Modified: 20 May 2021, 10:28 a.m.
Panel Version: 2.182
Provisionally associated with ?Microcephaly 14, primary, autosomal recessive #616402 (AR) in OMIM.
PMID: 24951542 - Khan et al 2014 - large consanguineous Pakistani family with 4 patients diagnosed with autosomal recessive primary microcephaly (MCPH). Sequencing of genes following homozygosity mapping identified a homozygous missense variant in HsSAS-6 (c.185T>C, p.Ile62Thr ). Analysed unaffected individuals were either heterozygous for this variant, or had two wild type alleles. All 4 affected individuals had severe microcephaly (occipitofrontal circumference ranged from -6.63 to -19.6 SD).
PMID: 30639237 - Zhang et al 2019 - report a non-consanguineous Chinese family in which two foetuses were identified with microcephaly. In the later pregnancy the foetus had a head circumference -4 SD at 24 weeks of gestation. Compound heterozygous splice variants in SASS6 were identified by WES ( c.127-13A>G and c.1867+2T>A), one inherited from each of the parents. RT-PCR confirmed the effect on splicing.
Created: 20 May 2021, 10:25 a.m. | Last Modified: 20 May 2021, 10:26 a.m.
Panel Version: 2.180
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
?Microcephaly 14, primary, autosomal recessive, OMIM:616402
As discussed with the GMS Neurology Specialist Test Group webex call 11thJuly 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Created: 29 Jul 2019, 4:18 p.m. | Last Modified: 29 Jul 2019, 4:18 p.m.
Panel Version: 1.62
PMID:24951542 (Khan et al., 2014) examined three affected individuals from a consanguineous MCPH family from Pakistan and identified a homozygous c.185T>C missense mutation in the SASS6 gene, resulting in a p.Ile62Thr substitution. The Ile62Thr mutant of SASS6 is substantially less efficient than the wild-type protein in sustaining centriole formation.
Created: 13 Dec 2016, 10:55 a.m.
Gene: sass6 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: SASS6 were changed from autosomal recessive primary microcephaly (MCPH); ?Microcephaly 14, primary, autosomal recessive, 616402 to ?Microcephaly 14, primary, autosomal recessive, OMIM:616402
Publications for gene: SASS6 were set to 24951542
Source NHS GMS was added to SASS6.
2nd March 2017: Panel review was assessed and panel was revised according to expert review and additional curation. This panel began with an expert gene list from Professor Andrew Jackson (University of Edinburgh) for primary microcephaly (MCPH) and microcephalic primordial dwarfism (MPD). Other disorders are included where microcephaly is a primary feature. Disorders where microcephaly is not the primary presenting feature are not included (e.g. congenital disorders of glycosylation, Proud syndrome, Norrie disease). The panel does not include disorders with a cortical malformation (e.g. lissencephaly) since the Malformations of cortical development' panel would be applied to these patients.
SASS6 was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Source: Other
SASS6 was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Literature
SASS6 was created by rfoulger