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Relevance to Autism

This gene has been associated with syndromic autism, where a subpopulation of individuals with Smith-Lemli-Opitz syndrome (SLOS) develop autism (Tierney et al., 2001).

Molecular Function

This gene encodes an enzyme that removes the C(7-8) double bond in the B ring of sterols and catalyzes the conversion of 7-dehydrocholesterol to cholesterol.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Behavior phenotype in the RSH/Smith-Lemli-Opitz syndrome.
Smith-Lemli-Opitz syndrome
ASD
Support
Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders.
ASD
Support
Integrating de novo and inherited variants in 42
ASD
Support
Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.
ID
Microcephaly
Support
Exploring the biological role of postzygotic and germinal de novo mutations in ASD
ASD
Support
Large-scale discovery of novel genetic causes of developmental disorders.
Hearing impairment
Support
Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.
ASD
Macrocephaly
Support
Abnormal serotonergic development in a mouse model for the Smith-Lemli-Opitz syndrome: implications for autism.
Support
Diagnostic Yields of Trio-WES Accompanied by CNVseq for Rare Neurodevelopmental Disorders.
Smith-Lemli-Opitz syndrome
Support
Genetic testing including targeted gene panel in a diverse clinical population of children with autism spectrum disorder: Findings and implications.
ASD
Support
Expanding the genetic heterogeneity of intellectual disability.
DD
Support
DD, epilepsy/seizures
Highly Cited
Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome.
Smith-Lemli-Opitz syndrome
Highly Cited
Molecular cloning and expression of the human delta7-sterol reductase.
Highly Cited
The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome.
Smith-Lemli-Opitz syndrome
ASD
Recent Recommendation
Social approach in genetically engineered mouse lines relevant to autism.
Recent Recommendation
Loss of apolipoprotein E exacerbates the neonatal lethality of the Smith-Lemli-Opitz syndrome mouse.
Recent Recommendation
Negative regulation of Hedgehog signaling by the cholesterogenic enzyme 7-dehydrocholesterol reductase.
Recent Recommendation
Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update.
Smith-Lemli-Opitz syndrome
Recent Recommendation
Modeling Smith-Lemli-Opitz syndrome with induced pluripotent stem cells reveals a causal role for Wnt/-catenin defects in neuronal cholesterol syn...

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN063R001a 
 stop_gained 
 c.452G>A 
 p.Trp151Ter 
 Familial 
 Maternal 
 Simplex 
 GEN063R001b 
 missense_variant 
 c.976G>T 
 p.Val326Leu 
 Familial 
 Paternal 
 Simplex 
 GEN063R002a 
 stop_gained 
 c.452G>A 
 p.Trp151Ter 
 Familial 
 Maternal 
 Simplex 
 GEN063R002b 
 missense_variant 
 c.976G>T 
 p.Val326Leu 
 Unknown 
 Not maternal 
 Simplex 
 GEN063R003a 
 stop_gained 
 c.452G>A 
 p.Trp151Ter 
 Unknown 
  
 Multiplex 
 GEN063R003b 
 missense_variant 
 c.1130G>C 
 p.Cys380Ser 
 Unknown 
  
 Multiplex 
 GEN063R004a 
 missense_variant 
 c.278C>T 
 p.Thr93Met 
 Unknown 
  
  
 GEN063R004b 
 frameshift_variant 
 c.627-642del 
  
 Unknown 
  
  
 GEN063R005a 
 missense_variant 
 c.296T>C 
 p.Leu99Pro 
 Unknown 
  
  
 GEN063R005b 
 splice_site_variant 
 IVS8-1G>C 
 p.? 
 Unknown 
  
  
 GEN063R006a 
 missense_variant 
 c.151C>T 
 p.Pro51Ser 
 Unknown 
 Not maternal 
 Simplex 
 GEN063R006b 
 splice_site_variant 
 IVS8-1G>C 
 p.? 
 Familial 
 Maternal 
 Simplex 
 GEN063R007a 
 stop_gained 
 c.452G>A 
 p.Trp151Ter 
 Familial 
 Paternal 
  
 GEN063R007b 
 missense_variant 
 c.470T>C 
 p.Leu157Pro 
 Familial 
 Maternal 
  
 GEN063R008a 
 missense_variant 
 c.740C>T 
 p.Ala247Val 
 Familial 
 Maternal 
 Simplex 
 GEN063R008b 
 missense_variant 
 c.1210C>T 
 p.Arg404Cys 
 Familial 
 Paternal 
 Simplex 
 GEN063R009a 
 missense_variant 
 c.296T>C 
 p.Leu99Pro 
 Unknown 
  
  
 GEN063R009b 
 missense_variant 
 c.1228G>A 
 p.Gly410Ser 
 Unknown 
  
  
 GEN063R010a 
 missense_variant 
 c.976G>T 
 p.Val326Leu 
 Familial 
 Paternal 
  
 GEN063R010b 
 missense_variant 
 c.1054C>T 
 p.Arg352Trp 
 Familial 
 Maternal 
  
 GEN063R011 
 missense_variant 
 c.976G>T 
 p.Val326Leu 
 Unknown 
  
  
 GEN063R012 
 missense_variant 
 c.976G>T 
 p.Val326Leu 
 Unknown 
  
  
 GEN063R013 
 missense_variant 
 c.1054C>T 
 p.Arg352Trp 
 Unknown 
  
  
 GEN063R014a 
 splice_site_variant 
 c.214-1G>C 
 p.? 
 Familial 
 Maternal 
 Simplex 
 GEN063R014b 
 missense_variant 
 c.269A>G 
 p.His90Arg 
 Familial 
 Paternal 
 Simplex 
 GEN063R015a 
 missense_variant 
 c.278C>T 
 p.Thr93Met 
 Familial 
 Both parents 
 Multiplex 
 GEN063R016 
 stop_gained 
 c.82C>T 
 p.Gln28Ter 
 Familial 
  
 Simplex 
 GEN063R017 
 missense_variant 
 c.1168C>T 
 p.His390Tyr 
 Familial 
  
 Simplex 
 GEN063R018 
 missense_variant 
 c.940C>A 
 p.Leu314Met 
 Familial 
  
 Simplex 
 GEN063R019a 
 missense_variant 
 c.778C>T 
 p.Arg260Trp 
 Familial 
 Both parents 
 Simplex 
 GEN063R020 
 splice_site_variant 
 c.964-1G>C 
  
 Unknown 
  
  
 GEN063R021a 
 missense_variant 
 c.278C>T 
 p.Thr93Met 
 Familial 
  
  
 GEN063R021b 
 missense_variant 
 c.907G>A 
 p.Gly303Arg 
 Familial 
  
  
 GEN063R022 
 stop_gained 
 c.16C>T 
 p.Gln6Ter 
 Familial 
 Maternal 
 Simplex 
 GEN063R023 
 missense_variant 
 c.1370G>A 
 p.Arg457Gln 
 De novo 
  
 Simplex 
 GEN063R024 
 synonymous_variant 
 c.1203C>T 
 p.Gly401%3D 
 De novo 
  
 Multiplex 
 GEN063R025a 
 missense_variant 
 c.1328G>A 
 p.Arg443His 
 Familial 
 Both parents 
  
  et al.  

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
11
Deletion
 3
 
11
Duplication
 3
 
11
Deletion-Duplication
 17
 

Model Summary

Underlying dysfunction of the 5-HT2A receptors that warrants further investigation to establish how this may related to behavioral disturbances in human patients carrying Dhcr7 mutations.

References

Type
Title
Author, Year
Additional
Biochemical, phenotypic and neurophysiological characterization of a genetic mouse model of RSH/Smith--Lemli--Opitz syndrome.
Primary
7-Dehydrocholesterol-dependent proteolysis of HMG-CoA reductase suppresses sterol biosynthesis in a mouse model of Smith-Lemli-Opitz/RSH syndrome.
Primary
Behavioral and serotonergic response changes in the Dhcr7-HET mouse model of Smith-Lemli-Opitz syndrome.

M_DHCR7_3_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted homologous recombination to delete coding exons III, IV and part of exon V of Dhcr7 gene.
Allele Type: Targeted (Knock out)
Strain of Origin: C57/B6
Genetic Background: Not Specified
ES Cell Line: J1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_DHCR7_4_HT

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted homologous recombination to delete coding exons III, IV and part of exon V of Dhcr7 gene.
Allele Type: Targeted (Knock out)
Strain of Origin: C57/B6
Genetic Background: Not Specified
ES Cell Line: J1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_DHCR7_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Deleting the last exon (exon 8) and the flanking splice acceptor site of the Dhcr7 gene.
Allele Type: Targeted (Knock out)
Strain of Origin: 129Ola
Genetic Background: C57B1/6
ES Cell Line: E14TG2a
Mutant ES Cell Line: Not Specified
Model Source: Resrouce Centre/Primary Database (B

M_DHCR7_2_KO_HT

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Deleting the last exon (exon 8) and the flanking splice acceptor site of the Dhcr7 gene.
Allele Type: Targeted (Knock out)
Strain of Origin: 129Ola
Genetic Background: C57B1/6
ES Cell Line: E14TG2a
Mutant ES Cell Line: Not Specified
Model Source: Resrouce Centre/Primary Database (B

M_DHCR7_1_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: .
Allele Type: Targeted (Deletino)
Strain of Origin: Not specified
Genetic Background: C57B1/6J
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_DHCR7_3_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Decreased
Description: Mutant mice have reduced movement and hypotonia
Exp Paradigm: General observations
 General observations
 Unreported
Brain size1
Decreased
Description: Smaller brain size; no increased apoptosis
Exp Paradigm: General observation; tdt-mediated dutp nick end-labeling (tunel) assay
 Tunel assay
 Unreported
Action potential property: firing rate1
Decreased
Description: Single action potential fired for depolarizing current
Exp Paradigm: Whole-cell recordings from cortical neurons in brain slices
 Whole-cell patch clamp
 24 hours
Neuroreceptor activity1
Decreased
Description: Reduced inward current induced by glutamate
Exp Paradigm: Whole-cell recordings from cortical neurons in brain slices
 Whole-cell patch clamp
 P1
Ion influx and permeability: sodium1
Abnormal
Description: Sodium current elicited in response to voltage step
Exp Paradigm: Whole-cell recordings from cortical neurons in brain slices
 Whole-cell patch clamp
 24 hours
Bioactive compound levels1
Increased
Description: Increased serum and tissue levels of 7-dehdyrocholesterol
Exp Paradigm: 7-dhc and 7-dhd accumulation
 Thin layer chromatography (tlc)
 E12.5-p0
Bioactive compound levels1
Decreased
Description: Decreased serum and tissue levels of cholesterol is found in mutants
Exp Paradigm: 7-dhc and 7-dhd accumulation
 Thin layer chromatography (tlc)
 E12.5-p0
Hormone levels1
Decreased
Description: Decreased sterol concentration; increased 7-dhc and 8-dhc levels; decreased desmosterol levels; decreased reduction of ergosterol to brassicasterol
Exp Paradigm: Gas chromatography/mass spectrometry
 Gas chromatography-mass spectrometry (gc-ms)
 Unreported
Skeletal development: craniofacial1
Decreased
Description: Mutant mice have deficient craniofacial development leading to a cleft palate and nasal plug
Exp Paradigm: General observations
 General observations
 Unreported
Size/growth1
Decreased
Description: Mutant mice have problems in feeding and reduced intrauterine growth
Exp Paradigm: General observations
 General observations
 Unreported
Size/growth1
Decreased
Description: Decreased size/growth; intra-uterine growth retardation
Exp Paradigm: General observations
 General observations
 Unreported
Mortality/lethality1
Increased
Description: Increased lethality
Exp Paradigm: General observations
 General observations
 P1
Gene expression1
 No change
 Quantitative pcr (qrt-pcr)
 Unreported
Protein expression level evidence1
 No change
 Western blot
 Unreported
Ion influx and permeability: chlorine1
 No change
 Whole-cell patch clamp
 P1
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_DHCR7_4_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hormone levels1
 No change
 Gas chromatography-mass spectrometry (gc-ms)
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_DHCR7_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Decreased
Description: There is lack of motor activity in the dhcr7 null mice
Exp Paradigm: General observations
 General observations
 Unreported
Respiratory function1
Decreased
Description: Respiratory function is significantly reduced in null mice leading to labored breathing and blue coloration in the animals
Exp Paradigm: General observations
 General observations
 Unreported
Renal function1
Decreased
Description: Renal function is significantly reduced leading to distended urinary bladder
Exp Paradigm: General observations
 General observations
 Unreported
Hormone levels1
Decreased
Description: There is significant reduction in total cholesterol and sterol concentration
Exp Paradigm: Capillary gas chromotography (gc) from liver and brain homogenates
 Gas chromotography (gc)
 Unreported
Skeletal development: craniofacial1
Decreased
Description: There is significant deficiency in craniofacial development leading to cleft palate
Exp Paradigm: General observations
 General observations
 Unreported
Mortality/lethality1
Increased
Description: Increased lethality
Exp Paradigm: General observations
 General observations
 P0-p1
Enzyme activity1
Decreased
Description: Reduced hmg-coa reductase activity
Exp Paradigm: Hmg-coa reductase activity
 Western blot
 Unreported
Enzyme activity1
Decreased
Description: Decreased 7dhc enzyme activity
Exp Paradigm: Enzyme activity
 Enzyme assay
 Unreported
Regulation of translation1
Decreased
Description: Decreased dhcr7 protein regulation
Exp Paradigm: Protein regulation
 Western blot
 Unreported
Regulation of gene expression1
Decreased
Description: Decreased gene regulation
Exp Paradigm: Gene regulation
 Quantitative pcr (qrt-pcr)
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_DHCR7_2_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Enzyme activity1
Decreased
Description: Decreased 7hdc enzyme activity
Exp Paradigm: Enzyme activity
 Enzyme assay
 Unreported
General characteristics1
 No change
 General observations
 Unreported
Enzyme activity1
 No change
 Western blot
 Unreported
Hormone levels1
 No change
 Gas chromotography (gc)
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_DHCR7_1_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Head twitch response1
Increased
Description: Increased 5-ht receptor sensitivity indicated by greater head twitch response after administration of serotonergic agonist doi
Exp Paradigm: Doi-induced head twitch response
 Head twitch response
 6, 12 months
Social dominance1
Increased
Description: Increased social dominance indicated by more bouts won against unfamiliar mice
Exp Paradigm: Male mice: tube test for social dominance
 Tube test of social dominance
 3 months
Social dominance1
Increased
Description: Increased social dominance indicated by more bouts won against unfamiliar mice
Exp Paradigm: Female mice: tube test for social dominance
 Tube test of social dominance
 12 months
Core body temperature1
Increased
Description: Increaed 5-ht receptor sensitivity as indicated by increased core body temperature decrease following 8-oh-dpat administration with greater effect in male vs. female
Exp Paradigm: 8-oh-dpat induced hypothermia
 Body temperature measurement
 12 months
Anxiety1
 No change
 Elevated zero maze test
 6 months
Spatial working memory1
 No change
 Y-maze test
 6 months
Grip strength1
 No change
 Inverted grid test
 6 months
Motor coordination and balance1
 No change
 Accelerating rotarod test
 6 months
Head bobbing1
 No change
 Hole-board test
 6 months
Repetitive digging1
 No change
 Marble-burying test
 6 months
Social approach1
 No change
 Olfactory discrimination test
 6 months
Social dominance1
 No change
 Tube test of social dominance
 3 months
Social dominance1
 No change
 Tube test of social dominance
 12 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Seizure





Download DHCR7's Cytoscape file


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