Human Gene Module / Chromosome 17 / SGSH

SGSHN-sulfoglucosamine sulfohydrolase

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
4 / 9
Rare Variants / Common Variants
10 / 0
Aliases
SGSH, HSS,  MPS3A,  SFMD
Associated Syndromes
-
Chromosome Band
17q25.3
Associated Disorders
ID, ASD
Relevance to Autism

In a recent report, 13 of 21 children with mucopolysaccharidosis type IIIA (MPS IIIA), documented enzyme deficiency and SGSH gene mutations that were evaluated with the Autism Diagnostic Observation Schedule (ADOS) (module 1) met the ADOS criteria for ASD/autism (Rumsey et al., 2014).

Molecular Function

This gene encodes one of several enzymes involved in the lysosomal degradation of heparan sulfate. Mutations in this gene are associated with Sanfilippo syndrome A, one type of the lysosomal storage disease mucopolysaccaridosis III, which results from impaired degradation of heparan sulfate [MPS IIIA; MIM:252900].

External Links
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Human
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Mouse
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SFARI Genomic Platforms
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Reports related to SGSH (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support [Hyperactivity and behavioral disorders in Sanfilippo A (mucopolysaccharidosis type IIIA)--case report and review of the literature] Wolaczyk T , et al. (2001) No -
2 Recent Recommendation Mucopolysaccharidosis type III (Sanfilippo syndrome) and misdiagnosis of idiopathic developmental delay, attention deficit/hyperactivity disorder or autism spectrum disorder Wijburg FA , et al. (2013) No -
3 Recent Recommendation Sanfilippo type A: new clinical manifestations and neuro-imaging findings in patients from the same family in Israel: a case report Sharkia R , et al. (2014) No ID
4 Primary Acquired autistic behaviors in children with mucopolysaccharidosis type IIIA Rumsey RK , et al. (2014) No ASD
5 Support Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes Xiong J , et al. (2019) Yes Mucopolysaccharidosis type IIIA, ID
6 Support - Chen S et al. (2021) Yes DD, ID
7 Support - Wang J et al. (2023) Yes -
8 Support - Sanchis-Juan A et al. (2023) No -
9 Support - Karen Lob et al. () Yes DD
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.97G>A p.Gly33Arg missense_variant Unknown - - 39136901 Karen Lob et al. ()
c.197C>G p.Ser66Trp missense_variant Unknown - - 39136901 Karen Lob et al. ()
c.734G>A p.Arg245His missense_variant Familial - - 31031587 Xiong J , et al. (2019)
c.479G>A p.Arg160Gln missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.734G>A p.Arg245His missense_variant Familial Maternal - 34800434 Chen S et al. (2021)
c.892T>C p.Ser298Pro missense_variant Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
c.653_654dup p.Asp219TrpfsTer46 frameshift_variant Familial - - 31031587 Xiong J , et al. (2019)
c.1272_1282del p.Tyr424Ter stop_gained Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
c.653_654dup p.Asp219TrpfsTer46 frameshift_variant Familial Paternal - 34800434 Chen S et al. (2021)
c.416C>T p.Thr139Met missense_variant Familial Both parents Multiplex 24576347 Sharkia R , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

13 of 21 children with mucopolysaccharidosis type IIIA (MPS IIIA), documented enzyme deficiency and SGSH gene mutations that were evaluated with the Autism Diagnostic Observation Schedule (ADOS) (module 1) met the ADOS criteria for ASD/autism (PMID 24582005). A homozygous missense variant in the SGSH gene (c.416C>T; p.T139M) was observed in two affected female siblings from a consanguineous Palestinian family who presented with intellectual disability, autistic features, and mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) (PMID 24576347).

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

13 of 21 children with mucopolysaccharidosis type IIIA (MPS IIIA), documented enzyme deficiency and SGSH gene mutations that were evaluated with the Autism Diagnostic Observation Schedule (ADOS) (module 1) met the ADOS criteria for ASD/autism (PMID 24582005). A homozygous missense variant in the SGSH gene (c.416C>T; p.T139M) was observed in two affected female siblings from a consanguineous Palestinian family who presented with intellectual disability, autistic features, and mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) (PMID 24576347).

Reports Added
[New Scoring Scheme]
4/1/2019
S
icon
S

Score remained at S

Description

13 of 21 children with mucopolysaccharidosis type IIIA (MPS IIIA), documented enzyme deficiency and SGSH gene mutations that were evaluated with the Autism Diagnostic Observation Schedule (ADOS) (module 1) met the ADOS criteria for ASD/autism (PMID 24582005). A homozygous missense variant in the SGSH gene (c.416C>T; p.T139M) was observed in two affected female siblings from a consanguineous Palestinian family who presented with intellectual disability, autistic features, and mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) (PMID 24576347).

Reports Added
[Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes.2019]
Krishnan Probability Score

Score 0.44183721899695

Ranking 18115/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.0001057899459397

Ranking 13054/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.76022064257884

Ranking 1661/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score -0.37791499683023

Ranking 18138/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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