Clefting
Gene: PTDSS1Comment on phenotypes: added phenotypes submitted by expert reviewerCreated: 1 Jun 2017, 7:42 a.m.
Comment on publications: Added publications 25363158; 26117586 from expert reviewCreated: 1 Jun 2017, 7:40 a.m.
Comment on mode of pathogenicity: added from expert reviewCreated: 1 Jun 2017, 7:39 a.m.
de novo gain-of-function mutations in PTDSS1 cause Lenz-Majewski syndrome (LMS - OMIM 151050). There is no evidence for a phenotype associated with loss-of-function mutations and knock out mice have no obvious phenotype. I have reviewed 16 published cases either with suspected LMS (n=6) or confirmed with a molecular diagnosis (n=10) and only one has been reported to have a cleft palate (PMID: 15194948). As commented elsewhere, this same mutation is found in two other LMS patients who do not have cleft palate. I concur that mutations in PTDSS1 are therefore unlikely to be a direct cause of cleft palate and there is little evidence at present to incorporate this gene on the clefting panel.Created: 1 Jun 2017, 7:28 a.m.
Phenotypes
progressive sclerosis and hyperostosis of skull, vertebra and tubular bones; growth restriction; broad prominent forehead; delayed closure of the fontanelles; brachydactyly of fingers and toes; proximal symphalangism cutis laxa; dental enamel hypoplasia; choanal atresia
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Comment on list classification: PMID: 24241535 - patient 3 (who was previously reported in PMID: 15194948), shares the same PTDSS1 variant as two other patients who did not have a cleft palate. Of the 5 patients reported with PTDSS1 variants, only one had a cleft palate. The authors suggest that patient 3 who displayed severe intellectual
disability as well as cleft palate, cranial nerve palsy and hydrocephalus (not observed in any of the other patients) may have additional variants in other genes that account for the variability in phenotype. Not enough evidence currently to make this gene green on the clefting panel. Confirms one case of ten have been reported with a cleft palate, and refer to PMID:24241535.Created: 31 May 2017, 3:20 p.m.
Comment on list classification: Confirmed DD gene for LENZ-MAJEWSKI HYPEROSTOTIC DWARFISM, however this does not mention clefting within the phenotypes. Clefting is not within the clinical synopsis for Lenz-Majewski hyperostotic dwarfism in OMIM, but a sporadic case is mentioned in the description on the phenotype page.Created: 31 May 2017, 3:05 p.m.
Comment on publications: PMID: 15194948 - a sporadic case of Lenz-Majewski syndrome (LMS) with newly recognized manifestations including facial palsy, cleft palate and hydrocephalus developing later in infancy.Created: 31 May 2017, 3:01 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Lenz-Majewski hyperostotic dwarfism 151050
Phenotypes for PTDSS1 were set to Lenz-Majewski hyperostotic dwarfism, 151050; progressive sclerosis and hyperostosis of skull, vertebra and tubular bones; growth restriction; broad prominent forehead; delayed closure of the fontanelles; brachydactyly of fingers and toes; proximal symphalangism cutis laxa; dental enamel hypoplasia; choanal atresia
Publications for PTDSS1 were set to 15194948; 24241535; 25363158; 26117586
Mode of pathogenicity for PTDSS1 was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panel reviews were assessed, and panel was revised according to reviews and further curation 31st May 2017
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
Publications for PTDSS1 were set to 15194948;24241535
This gene has been classified as Red List (Low Evidence).
Publications for PTDSS1 were set to 15194948
PTDSS1 was added to Cleftingpanel. Sources: Expert list
PTDSS1 was created by ellenmcdonagh