NM_002340.6(LSS):c.1547A>G (p.Asn516Ser) AND Alopecia-intellectual disability syndrome 4

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 10, 2022
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001034699.2

Allele description [Variation Report for NM_002340.6(LSS):c.1547A>G (p.Asn516Ser)]

NM_002340.6(LSS):c.1547A>G (p.Asn516Ser)

Gene:

LSS:lanosterol synthase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.3

Genomic location:

Preferred name:

NM_002340.6(LSS):c.1547A>G (p.Asn516Ser)

HGVS:

NC_000021.9:g.46206689T>C
NG_011510.1:g.27136A>G
NM_001001438.3:c.1547A>G
NM_001145436.2:c.1514A>G
NM_001145437.1:c.1307A>G
NM_001145437.2:c.1307A>G
NM_002340.6:c.1547A>GMANE SELECT
NP_001001438.1:p.Asn516Ser
NP_001138908.1:p.Asn505Ser
NP_001138909.1:p.Asn436Ser
NP_002331.3:p.Asn516Ser
NC_000021.8:g.47626603T>C
NM_002340.5:c.1547A>G

Protein change:

N436S; ASN516SER

Links:

OMIM: 600909.0010; dbSNP: rs148141905

NCBI 1000 Genomes Browser:

rs148141905

Molecular consequence:

NM_001001438.3:c.1547A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001145436.2:c.1514A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001145437.2:c.1307A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002340.6:c.1547A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Alopecia-intellectual disability syndrome 4
Synonyms:: ALOPECIA-MENTAL RETARDATION SYNDROME 4
Identifiers:: MONDO: MONDO:0030009; MedGen: C5394241; OMIM: 618840

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001197988	OMIM	no assertion criteria provided	Pathogenic (Feb 10, 2022)	germline	literature only	Besnard, T., Sloboda, N., Goldenberg, A., Kury, S., Cogne, B., Breheret, F., Trochu, E., Conrad, S., Vincent, M., Deb, W., Balguerie, X., Barbarot, S., and 27 others Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome. Genet. Med. 21: 2025-2035, 2019.

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001197988

OMIM

no assertion criteria provided

Pathogenic
(Feb 10, 2022)

germline

literature only

Besnard, T., Sloboda, N., Goldenberg, A., Kury, S., Cogne, B., Breheret, F., Trochu, E., Conrad, S., Vincent, M., Deb, W., Balguerie, X., Barbarot, S., and 27 others Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome. Genet. Med. 21: 2025-2035, 2019.

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Details of each submission

From OMIM, SCV001197988.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	not provided

Description

In 2 sisters (family 1) with complete alopecia and psychomotor retardation (APMR4; 618840), Besnard et al. (2019) identified compound heterozygosity for a c.1547A-G transition (c.1547A-G, NM_002340.5) in exon 16 of the LSS gene, resulting in an asn516-to-ser (N516S) substitution, and a c.2114C-A transversion in exon 22, resulting in a thr705-to-lys (T705K) substitution. Both substitutions involved highly conserved residues; the T705K mutation was not found in gnomAD, whereas the N516S variant was present at low frequency (8.157 x 10(-6)). Their parents were each heterozygous for 1 of the mutations.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 13, 2025

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