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Intellectual disability

Gene: RSPRY1

Amber List (moderate evidence)

RSPRY1 (ring finger and SPRY domain containing 1)
EnsemblGeneIds (GRCh38): ENSG00000159579
EnsemblGeneIds (GRCh37): ENSG00000159579
OMIM: 616585, Gene2Phenotype
RSPRY1 is in 4 panels

1 review

Catherine Snow (Genomics England)

Comment on list classification: Gene identified in literature PMID:30914295 as missing in PanelApp compared to other curated gene list for ID genes.

Faden et al (PMID: 26365341) reported on a consanguineous Bedouin Saudi family in which 4 sibs had progressive spondyloepimetaphyseal dysplasia, short stature, facial dysmorphism, short fourth metatarsals, and intellectual disability finding a a homozygous 1 bp duplication in RSPRY1 that predicts frameshift and premature truncation (GenBank: NM_133368.1; c.1279dupA [p.Thr427Asnfs∗10]

Using a "gene-matcher" tool they also studied a Peruvian boy with a homozygous missense variant (GenBank: NM_133368.1; c.121G>T [p.Gly41Cys]) in a conserved residue (GERP 5.22, Phast 658) in RSPRY1. The boy presented with a similar phenotype, who was born of parents from a small isolated region and presented with significant speech delay; he was diagnosed with autism spectrum disorder at 5 years of age. At age 8 years, he exhibited short stature, dysmorphic facial features, low-set ears, short trunk with hyperlordosis, varus and valgus knee deformities, and overriding toes. Skeletal survey showed delayed epiphyseal maturation, flattening of femoral heads, thoracic platyspondyly, and short fourth metatarsals.

Table 1 Faden et al (PMID: 26365341) all effected individuals are recorded as having ID.

The authors performed functional work on mice looking at limb abnormalities and found the expression of Rspry1 correlates strikingly with the skeletal defects observed in affected individuals and is also consistent with the presence of brain and craniofacial phenotypes, because expression was detected in embryonic and postnatal brain and in developing craniofacial tissues

Rating gene as Amber as only two unrelated cases reported.
Created: 30 May 2019, 2:27 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
  • Expert Review Amber
  • Literature
Phenotypes
  • Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, 616585
Tags
watchlist
OMIM
616585
Clinvar variants
Variants in RSPRY1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

25 Jul 2019, Gel status: 2

Added Tag

Catherine Snow (Genomics England)

Tag watchlist tag was added to gene: RSPRY1.

25 Jul 2019, Gel status: 2

Set mode of inheritance

Catherine Snow (Genomics England)

Mode of inheritance for gene RSPRY1 was changed from to BIALLELIC, autosomal or pseudoautosomal

25 Jul 2019, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Catherine Snow (Genomics England)

gene: RSPRY1 was added gene: RSPRY1 was added to Intellectual disability. Sources: Literature,Expert Review Amber Mode of inheritance for gene: RSPRY1 was set to Publications for gene: RSPRY1 were set to 26365341; 30914295 Phenotypes for gene: RSPRY1 were set to Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, 616585