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| Fetal anomalies v0.3151 | LRP6 |
Krithika Murali gene: LRP6 was added gene: LRP6 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: LRP6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LRP6 were set to 16126904; 30950205; 26387593; 26963285; 28813618; 29500247; 33164649; 34306029 Phenotypes for gene: LRP6 were set to Tooth agenesis, selective, 7 - MIM#616724; cleft lip/palate Review for gene: LRP6 was set to AMBER Added comment: LoF variants known to be associated with tooth agenesis. In addition, x2 unrelated families from 2 different studies with heterozygous LRP6 variant had tooth agenesis and cleft lip/palate (PMID 29500247; 26963285). Growth failure reported in some individuals but unclear if prenatal in onset (PMID 26963285). Minor finger/ear anomalies reported in x2 patients (PMID 26387593; 30950205)- unlikely to be detected antenatally and one of the reported patients (30950205) had x2 chromosome deletions, one of which involved LRP6 and multiple other genes. --- PMID: 34306029 Huang et al 2021 - Heterozygous LRP6: c.2570G > A (p.R857H), harbored by six members of a Chinese family, including 4 with tooth agenesis. Sparse hair another phenotypic feature. PMID: 33164649 Yu et al 2021 - identified 4 novel LRP6 heterozygous mutations in 4 of 77 oligodontia patients. One patient with a nonsense paternally inherited variant had a hypohidrotic ectodermal dysplasia phenotype - no antenatal features, father had oligodontia. Supportive functional evidence PMID: 29500247 Basha et al 2018 - Nonsense LRP6 variant identified in a family with cleft lip/palate. Proband had bilateral cleft lip and palate with missing upper lateral incisors, mother had bilateral cleft lip. x1 unaffected brother but family members not reassessed for oligodontia after variant identified. PMID: 28813618 Dinckan et al 2018 - heterozygous splice site LRP6 variant identified in 1 family with isolated tooth agenesis. Affected family members also had mild periocular hyperpigmentation and hypoplastic alae nasi - thought to be unrelated to phenotype PMID: 26963285 Ockeloen et al 2016 - frameshift variant identified in patient with tooth agenesis and orofacial clefting - boy born with bilateral cleft lip, L) sided cleft of the alveolus and complete cleft of the hard and soft palate. Also noted to have growth retardation, hypermetropia and small median alveolar manibular cleft. Maternal relatives with variant had severe tooth agenesis but no clefting. Canonical splice site variant identified in a patient with isolated severe tooth agenesis. Targeted resequencing showed statistically significant enrichment of unique LRP6 variants in tooth agenesis patients (7/67 versus 13/706 controls), not orofacial clefting cohort. 4/7 of these patients required growth hormone therapy and 3/7 had clinodactyly in addition to dental anomalies. PMID: 26387593 – Massink et al 2015 - x4 LoF heterozygous LRP6 variants identified in 4 unrelated families with isolated severe tooth agenesis. All affected members of one family showed minor anatomical variation of the ear and underdevelopment of the thumb PMID: 30950205 Ross et al 2019 - Proband with oligodontia and thrombocytopenia, also had mild finger and ear anomalies. Array revealed an interstitial loss of 150 kb in 8p23.1 encompassing MCPH1 and ANGPT2 and an interstitial loss of 290 kb in 12p13.2 encompassing ETV6, BCL2L14 and LRP6. Sources: Literature |
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| Fetal anomalies v0.2803 | MCPH1 | Zornitza Stark Marked gene: MCPH1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2803 | MCPH1 | Zornitza Stark Gene: mcph1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2803 | MCPH1 | Zornitza Stark Phenotypes for gene: MCPH1 were changed from MICROCEPHALY PRIMARY TYPE 1 to Microcephaly 1, primary, autosomal recessive, MIM# 251200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2802 | MCPH1 | Zornitza Stark Publications for gene: MCPH1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2801 | MCPH1 |
Zornitza Stark changed review comment from: Well established primary micorcephaly gene. Sources: Literature; to: Well established primary microcephaly gene. Sources: Literature |
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| Fetal anomalies v0.2801 | MCPH1 |
Zornitza Stark changed review comment from: Single individual reported as part of a CDH cohort. Sources: Literature; to: Well established primary micorcephaly gene. Sources: Literature |
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| Fetal anomalies v0.2801 | MCPH1 | Zornitza Stark edited their review of gene: MCPH1: Changed rating: GREEN; Changed phenotypes: Microcephaly 1, primary, autosomal recessive, MIM# 251200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | MCPH1 |
Zornitza Stark gene: MCPH1 was added gene: MCPH1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: MCPH1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MCPH1 were set to MICROCEPHALY PRIMARY TYPE 1 |
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