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Mendeliome

Gene: PRRX1

Green List (high evidence)

PRRX1 (paired related homeobox 1)
EnsemblGeneIds (GRCh38): ENSG00000116132
EnsemblGeneIds (GRCh37): ENSG00000116132
OMIM: 167420, Gene2Phenotype
PRRX1 is in 8 panels

2 reviews

Melanie Marty (Victorian Clinical Genetics Services)

Green List (high evidence)

Craniosynostosis (MONDO:0015469), PRRX1-related
> 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain.
> These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%.
> These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149)
> Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import.

Supporting evidence:
> Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454)

>Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651)

Agnathia-otocephaly complex, MIM# 202650
>Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708). Authors of the more recent publication on Craniosynostosis (PMID: 37154149) cast some doubt on the reports for Agnathia-otocephaly, possible explanations discussed are that this condition is AR and a 2nd hit was missed or another cause was not identified such as variants in OTX2.

> PMID: 7758948 generated a loss-of-function mutation in the mouse Pmx1 gene. Mice homozygous for the mutant allele died soon after birth and exhibited defects of skeletogenesis, which involved the loss or malformation of craniofacial, limb, and vertebral skeletal structures.
Created: 18 Jun 2024, 5:05 a.m. | Last Modified: 18 Jun 2024, 5:59 a.m.
Panel Version: 1.1840

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Craniosynostosis (MONDO:0015469), PRRX1-related

Publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Agnathia-otocephaly is a rare condition characterized by mandibular hypoplasia or agnathia, ventromedial auricular malposition (melotia) and/or auricular fusion (synotia), and microstomia with oroglossal hypoplasia or aglossia. Holoprosencephaly is the most commonly identified association, but skeletal, genitourinary, and cardiovascular anomalies, and situs inversus have been reported. The disorder is almost always lethal.

Three unrelated individuals reported with heterozygous LoF variants, one family with bi-allelic variants.
Created: 3 Dec 2021, 9:36 a.m. | Last Modified: 3 Dec 2021, 9:36 a.m.
Panel Version: 0.10055

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Agnathia-otocephaly complex, MIM# 202650

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Agnathia-otocephaly complex, MIM# 202650
OMIM
167420
Clinvar variants
Variants in PRRX1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

3 Dec 2021, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: prrx1 has been classified as Green List (High Evidence).

3 Dec 2021, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: PRRX1 were changed from to Agnathia-otocephaly complex, MIM# 202650

3 Dec 2021, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: PRRX1 were set to

3 Dec 2021, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: PRRX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: PRRX1 was added gene: PRRX1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: PRRX1 was set to Unknown