Hydrocephalus

Gene: P4HB

I don't know

PMID:25683117. 2 unrelated individuals (white) with multiple fractures, hydrocephalus, craniosynostosis, ocular proptosis, macrocephaly and distinct facial features. Both were heterozygous for the same variant (c.1178A>G, Y393C).

PMID:29384951. Chinese patient with microcephaly (-2 to -1 SD), ocular proptosis, frontal bossing, craniosynostosis, growth retardation, osteopenia and distinctive facial features. Patient did not have hydrocephalus or factures. Heterozygous for exon 5 - 8 deletion.

PMID:29263160. White patient with the same variant as the first 2 cases (c.1178A>G). Had fractures, ocular proptosis, failure to thrive and macrocephaly. Patient did not have hydrocephalus.

PMID:30063094. Thai patient with the same variant as bove (c.1178A>G). Patient had osteopenia, fractures, ocular proptosis and may have growth failure (weight < 3rd centile, length < 3rd centile). No macrocephlay or hydrocephalus.

This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype (probable). As only 2/5 patients have hydrocephalus this gene will be kept as Amber until more cases are available.

Created: 19 Jul 2021, 10:12 a.m. | Last Modified: 19 Jul 2021, 10:12 a.m.

Panel Version: 2.114

Green List (high evidence)

Four unrelated individuals reported with same recurrent de novo missense variant, p.Tyr393Cys, and an additional individual with de novo intragenic deletion of exons 5-8.

Created: 8 Aug 2020, 1:11 a.m. | Last Modified: 8 Aug 2020, 1:11 a.m.

Panel Version: 2.5

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cole-Carpenter syndrome 1, MIM#112240

Publications

• 30063094
• 29263160
• 25683117
• 29384951

Variants in this GENE are reported as part of current diagnostic practice

I don't know

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 Amber

Created: 29 Jul 2019, 2:49 p.m. | Last Modified: 29 Jul 2019, 2:49 p.m.

Panel Version: 1.34

I don't know

Only two unrelated cases to date, with the same mutation. Amber and watchlist at present

Created: 9 May 2017, 1:23 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Cole-Carpenter syndrome 1

Publications

• 25683117