Rare syndromic craniosynostosis or isolated multisuture synostosis
Gene: MASP1
Craniosynostosis was absent in the patient reported from Turkey in PMID:33765348 with MASP1-related 3MC syndrome. However, the literature review reported that nine of 29 previously reported cases had craniosynostosis. Tooze et al (PMID:36980886) reviewed that this gene should be green on this panel based on this evidence. However, recent review from Helen Lord (Oxford Medical Genetics Laboratories) and recommendation from NHS Genomic Medicine Service suggest that this gene should remain amber based on current evidence.Created: 24 Jul 2023, 12:02 p.m. | Last Modified: 24 Jul 2023, 12:02 p.m.
Panel Version: 4.170
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
3MC syndrome 1, OMIM:257920
Publications
1 case of craniosynostosis with a hom variant in MASP1 - Rooryck et al 2011 (21258343)
1 case with bilateral coronal synostosis - clinical diagnosis no molecular diagnosis in this paper- Guion-Almedia et al 1995 (7677137)
1 case of craniosynostosis reported in a patient with a VUS in MASP1 p.(Arg119Gln) (mat inhertied) also has a variant in MEGF8 - no information if variant hom or het... Clarke et al, 2018 (29168297).
Keep as amber not enough evidence to reclassify as greenCreated: 7 Jan 2022, 3:02 p.m. | Last Modified: 7 Jan 2022, 3:02 p.m.
Panel Version: 2.60
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Craniosynostosis occurs in 20-30% of individuals with 3MC syndrome. Other syndromes have been included in this panel, where CSS is a very rarely reported feature.Created: 3 Jul 2020, 3:57 a.m. | Last Modified: 3 Jul 2020, 3:57 a.m.
Panel Version: 2.9
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
3MC syndrome
Publications
Variants in this GENE are reported as part of current diagnostic practice
CSS occurs in 20-30% of 3MC cases (which also includes COLEC11, MASP1). One case with MASP1 and CSS reported by Rooryck. 2 additional cases with abnormal skull shape reported by Urquhart et al. Not convinced meets green criteria based on published cases (AW) ; Review on behalf of Tracy Lester and Andrew WilkieCreated: 5 Mar 2019, 11:33 a.m.
Phenotypes
3MC syndrome 1 - 257920
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed. It has been agreed that this gene should remain amber at this time.Created: 5 Mar 2022, 6:18 p.m. | Last Modified: 5 Mar 2022, 6:18 p.m.
Panel Version: 2.65
Comment on list classification: Promoting from red to amber but with a green recommendation for GMS review. Publications from Basdemirci et al and Atik et al suggest further cases where craniosynostosis is a feature.Created: 22 Jul 2021, 10:21 p.m. | Last Modified: 22 Jul 2021, 10:21 p.m.
Panel Version: 2.40
Checking for further reported cases:
PMID: 30601195 - Basdemirci et al 2019 - 3 siblings with 3MC syndrome in which a novel homozygous missense mutation, p.V704G, in MASP1 was identified in 2 of the siblings (not clear if the 3rd sibling was analysed). Craniosynostosis/skull asymmetry is reported in 2 siblings but no details given.
PMID: 29407414 - Graul-Neumann et al 2018 - 1adult female with a homozygous 2kb deletion, partially affecting exon 12 of MASP1 found by trio exome sequencing. She has the characteristic facial gestalt and typical multiple congenital anomalies but lacking the key feature cleft lip and palate. At birth craniofacial dysmorphism with skull asymmetry, open sutura metopica and facial asymmetry were noted among other features.
PMID: 26419238 - Atik et al 2015 - report on 6 unrelated children with 3MC1 syndrome. Sanger sequencing of MASP1 found 2 different splice site variants, and 3 different missense variants in the 6 probands. Two are reported to have craniosynostosis/skull asymmetry but no details given.
No mention of craniosynostosis or skull asymmetry:
PMID: 21035106 - Sirmaci et al 2010 - 3 individuals from 2 consanguineous Turkish families with 3MC. A missense and nonsense mutation in MASP1 were found by WES and Sanger sequencing in the two families respectively. Craniosynostosis is NOT mentioned as part of the phenotype.Created: 22 Jul 2021, 10:12 p.m. | Last Modified: 22 Jul 2021, 10:12 p.m.
Panel Version: 2.36
PMID: 21258343 - Rooryck et al 2011 - report 1 patient with a homozygous MASP1variant ( c.1489 C>T, p.His497Tyr) that segregated with 3MC syndrome in the family. The patient's features included craniosynostosis.
PMID: 26789649 - Urquhart et al 2016 - report two 3MC syndrome patients with homozygous variants in MASP1 (c.760A>T,p.(Leu 254*) and c.547G>T, p(.Val 183Leu) ) who have plagiocephaly and turricephaly respectively, but they note that craniosynostosis was not observed.Created: 10 Nov 2019, 11:10 p.m. | Last Modified: 10 Nov 2019, 11:15 p.m.
Panel Version: 2.0
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: MASP1; Suggested initial gene rating: amberCreated: 5 Mar 2019, 11:21 a.m.
Publications
Tag Q3_21_rating was removed from gene: MASP1.
Gene: masp1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: MASP1 were changed from 3MC syndrome 1 257920 to 3MC syndrome 1, OMIM:257920; 3MC syndrome 1, MONDO:0009770
Publications for gene: MASP1 were set to
Mode of inheritance for gene: MASP1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Tag Q2_21_rating was removed from gene: MASP1. Tag Q3_21_rating tag was added to gene: MASP1.
Tag Q2_21_rating tag was added to gene: MASP1.
Added phenotypes 3MC syndrome 1 257920 for gene: MASP1
gene: MASP1 was added gene: MASP1 was added to Craniosynostosis. Sources: NHS GMS Mode of inheritance for gene: MASP1 was set to