Severe microcephaly

Gene: CRIPT

Amber List (moderate evidence)

CRIPT (CXXC repeat containing interactor of PDZ3 domain)
EnsemblGeneIds (GRCh38): ENSG00000119878
EnsemblGeneIds (GRCh37): ENSG00000119878
OMIM: 604594, Gene2Phenotype
CRIPT is in 4 panels

1 review

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating to Amber. Borderline gene: 3 cases of CRIPT mutations causing microcephaly, but one case (in PMID:24389050) is inferred based on the genotype of the (first-cousin) parents because DNA wasn't available from the deceased patient.
7 Feb 2017, 10:44 a.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Other
Phenotypes
  • Short stature with microcephaly and distinctive facies, 615789
OMIM
604594
Clinvar variants
Variants in CRIPT
Penetrance
Complete
Publications
  • 27250922 Leduc et al., 2016 describe a female with biallelic mutations in CRIPT, presenting with short stature, dysmorphic features, microcephaly and hypopigmented macules. They detect a c.8G>A (p.C3Y) missense variant inherited from the mother in exon 1, and a 1,331?bp deletion encompassing exon 1, inherited from the father
  • 24389050 Shaheen et al., 2014 report 2 cases: they examined cases with Short stature with microcephaly and distinctive facies (OMIM:615789). In a 3 year old boy they identified homozygosity for a 2bp insertion (c.133_134insGG) predicted to cause premature termination (Ala45GlyfsTer87). They also analyzed DNA from the first-cousin parents of a deceased affected male Saudi Arabian infant. The patient was presumed homozygous for a loss of function variant based on the heterozygous status of the parents.
Panels with this gene

History Filter Activity

2 Mar 2017, Gel status: 2

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

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.

7 Feb 2017, Gel status: 2

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Amber List (Moderate Evidence).

17 Jan 2017, Gel status: 2

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Amber List (Moderate Evidence).

17 Jan 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for CRIPT were set to 27250922 Leduc et al., 2016 describe a female with biallelic mutations in CRIPT, presenting with short stature, dysmorphic features, microcephaly and hypopigmented macules. They detect a c.8G>A (p.C3Y) missense variant inherited from the mother in exon 1, and a 1,331?bp deletion encompassing exon 1, inherited from the father; 24389050 Shaheen et al., 2014 report 2 cases: they examined cases with Short stature with microcephaly and distinctive facies (OMIM:615789). In a 3 year old boy they identified homozygosity for a 2bp insertion (c.133_134insGG) predicted to cause premature termination (Ala45GlyfsTer87). They also analyzed DNA from the first-cousin parents of a deceased affected male Saudi Arabian infant. The patient was presumed homozygous for a loss of function variant based on the heterozygous status of the parents.

17 Jan 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

CRIPT was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Other

17 Jan 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

CRIPT was created by rfoulger