Severe microcephaly
Gene: CRIPTEnsemblGeneIds (GRCh38): ENSG00000119878
EnsemblGeneIds (GRCh37): ENSG00000119878
OMIM: 604594, Gene2Phenotype
CRIPT is in 10 panels
3 reviews
Ida Ertmanska (Genomics England Curator)
Comment on list classification: There are now 6 unrelated individuals reported in literature with biallelic CRIPT variants and Rothmund-Thomson syndrome, with microcephalic dwarfism being a consistent feature. Hence, this gene can be promoted to Green at the next update.Created: 11 Sep 2026, 1:27 p.m. | Last Modified: 11 Sep 2026, 1:27 p.m.
Panel Version: 9.31
PMID: 37013901 Averdunk et al., 2023
Report of 2 probands diagnosed with Rothmund-Thomson syndrome, harbouring biallelic CRIPT variants.
P1 - 4yo Moroccan female, homozygous for CRIPT: c.132del, p.Ala45Glnfs*86
P2 - 8yo Romanian male homozygous for CRIPT: c.227G>A, p.(Cys76Tyr)
Both patients had facial rash, poikiloderma, sparse hair, short stature, syndactyly of toes, seizures, abnormal teeth, developmental delay, recurrent chest infections; P1 also had cataracts, dystrophic nails, and a proximally placed thumb; only P2 had microcephaly.
Also includes literature review of previously reported patients (PMID: 36630262 Akalın et al., 2023; PMID: 27250922 Leduc et al., 2016; PMID: 24389050 Shaheen et al., 2014) - 4 unrelated probands with unique biallelic CRIPT variants: hmz c.133_134insGG, p.(Ala45Glyfs∗82); hmz c.141del p.(Phe47Leufs∗84); comp het c.8G>A p.(Cys3Tyr) & 1,331 bp del exon 1; hmz c.7_8del; p.(Cys3Argfs∗4).
2 individuals were from Saudi Arabia, one from Turkey, and one African American.
Phenotype: facial rash (3/4), poikiloderma (2/4), short stature (4/4), sparse hair (3/4), Osteopenia/metaphyseal striations (4/4), dystrophic nails (1/4), syndactyly of toes 4&5 (4/4), proportional microcephaly (4/4), dev delay (4/4), recurrent chest infections (4/4), anemia (3/4), variable retinal defects (4/4), abnormal teeth (2/4), scoliosis (4/4), 11 pairs of ribs (2/4).
None of the patients had cataracts.
Microcephaly severity: PMID: 27250922 head circumference was 47 cm (Z=−2.7) at 4 yrs. PMID: 24389050: individuals had head circumference of 45 cm (-2.5SD) and 35 cm (-2.7 SD) respectively at time of report. PMID: 36630262 - proband OFC was 44cm at last evaluation (-4.63 SDS).Created: 11 Sep 2026, 11:09 a.m. | Last Modified: 11 Sep 2026, 11:09 a.m.
Panel Version: 9.28
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Rothmund-Thomson syndrome, type 3, OMIM:615789; Rothmund-Thomson syndrome type 3, MONDO:0014347
Publications
Louise Daugherty (Genomics England Curator)
As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene AmberCreated: 29 Jul 2019, 4:18 p.m. | Last Modified: 29 Jul 2019, 4:18 p.m.
Panel Version: 1.62
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.Created: 7 Feb 2017, 10:44 a.m.
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- NHS GMS
- Expert Review Amber
- Other
- Phenotypes
-
- Rothmund-Thomson syndrome, type 3, OMIM:615789
- Rothmund-Thomson syndrome type 3, MONDO:0014347
- Tags
- OMIM
- 604594
- Clinvar variants
- Variants in CRIPT
- Penetrance
- Complete
- Publications
- Panels with this gene
History Filter Activity
Added Tag
Ida Ertmanska (Genomics England Curator)Tag Q3_26_promote_green tag was added to gene: CRIPT.
Set Phenotypes
Ida Ertmanska (Genomics England Curator)Phenotypes for gene: CRIPT were changed from Ida Ertmanska (Genomics England Curator) Rothmund-Thomson syndrome, type 3, OMIM:615789; Rothmund-Thomson syndrome type 3, MONDO:0014347 to Rothmund-Thomson syndrome, type 3, OMIM:615789; Rothmund-Thomson syndrome type 3, MONDO:0014347
Set Phenotypes
Ida Ertmanska (Genomics England Curator)Phenotypes for gene: CRIPT were changed from Short stature with microcephaly and distinctive facies, 615789 to Ida Ertmanska (Genomics England Curator) Rothmund-Thomson syndrome, type 3, OMIM:615789; Rothmund-Thomson syndrome type 3, MONDO:0014347
Set publications
Ida Ertmanska (Genomics England Curator)Publications for gene: 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.
Added New Source
Louise Daugherty (Genomics England Curator)Source NHS GMS was added to CRIPT.
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.
Gene classified by Genomics England curator
Rebecca Foulger (Genomics England curator)This gene has been classified as Amber List (Moderate Evidence).
Gene classified by Genomics England curator
Rebecca Foulger (Genomics England curator)This gene has been classified as Amber List (Moderate Evidence).
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.
Added New Source
Rebecca Foulger (Genomics England curator)CRIPT was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Other
Created
Rebecca Foulger (Genomics England curator)CRIPT was created by rfoulger