Severe microcephaly

Gene: POC1A

Green List (high evidence)

POC1A (POC1 centriolar protein A)
EnsemblGeneIds (GRCh38): ENSG00000164087
EnsemblGeneIds (GRCh37): ENSG00000164087
OMIM: 614783, Gene2Phenotype
POC1A is in 9 panels

1 review

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Red to Green after discussion with Arianna Tucci: On expert list from Andrew Jackson. >3 cases for SOFT syndrome. Although SOFT syndrome is not a microcephalic primoridal dwarfism (PD), still considered in the PD spectrum.
2 Mar 2017, 11:31 a.m.
PMID:26374189 (Barraza-García et al., 2016) identify two novel homozygous POC1A mutations in two individuals (a Spanish boy and a Moroccan boy) with primordial dwarfism (SOFT syndrome, MIM:614813). The truncating mutations were a frameshift c254delT and c515G>A (Trp172*). Parents were heterozygous carriers of the mutations and were most likely related in both families.
27 Feb 2017, 4:57 p.m.
Koparir et al., 2015 (PMID:26162852) identified a novel homozygous p.T120A missense mutation in POC1A in 2 related patients with primordial dwarfism.
27 Feb 2017, 4:53 p.m.
PMID:26791357 (Ko et al., 2016) report an 8.5-year-old boy with SOFT syndrome showing primordial dwarfism and with compound heterozygous variants in POC1A.
27 Feb 2017, 4:49 p.m.
PMID:22840363: In 8 affected members of 2 consanguineous Israeli families of Arab Muslim origin with short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (OMIM:614813) Sarig et al. (2012) identified homozygosity for a 512T-C (L171P) transition in POC1A.
27 Feb 2017, 4:49 p.m.
PMID:22840364: In 5 children with primordial dwarfism and distinctive facial features (OMIM:614813) from 3 consanguineous Saudi families, Shaheen et al. (2012) identified homozygosity for a 241C-T (R81X) transition in POC1A. This is likely a founder mutation.
27 Feb 2017, 4:48 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
  • Expert list
Phenotypes
  • MCPH
  • primary microcephaly
  • Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, 614813
  • Microcephaly in adulthood
  • primordial dwarfism
  • SOFT syndrome
OMIM
614783
Clinvar variants
Variants in POC1A
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

2 Mar 2017, Gel status: 4

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.

2 Mar 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

27 Feb 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for POC1A were set to 22840364; 22840363; 26374189; 26791357

27 Feb 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for POC1A were set to MCPH; primary microcephaly; Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, 614813; Microcephaly in adulthood; primordial dwarfism; SOFT syndrome

17 Jan 2017, Gel status: 1

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Red List (Low Evidence).

17 Jan 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for POC1A were set to 22840364: In 5 children with primordial dwarfism and distinctive facial features (OMIM:614813) from 3 consanguineous Saudi families, Shaheen et al. (2012) identified homozygosity for a 241C-T (R81X) transition in POC1A. This is likely a founder mutation; 22840363: In 8 affected members of 2 consanguineous Israeli families of Arab Muslim origin with short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (OMIM:614813) Sarig et al. (2012) identified homozygosity for a 512T-C (L171P) transition in POC1A.

17 Jan 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for POC1A were set to 22840364: In 5 children with primordial dwarfism and distinctive facial features (OMIM:614813) from 3 consanguineous Saudi families, Shaheen et al. (2012) identified homozygosity for a 241C-T (R81X) transition in POC1A.; 22840363: In 8 affected members of 2 consanguineous Israeli families of Arab Muslim origin with short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (OMIM:614813) Sarig et al. (2012) identified homozygosity for a 512T-C (L171P) transition in POC1A.

13 Dec 2016, Gel status: 0

Set Mode of Inheritance, Added New Source

Rebecca Foulger (Genomics England curator)

POC1A was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Source: Other Model of inheritance for gene POC1A was set to BIALLELIC, autosomal or pseudoautosomal

13 Dec 2016, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

POC1A was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Expert list

13 Dec 2016, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

POC1A was created by rfoulger