Details of Disease

Disease Name

Meckel syndrome, type 1

Dysencephalia Splanchnocystica; Meckel syndrome; Meckel syndrome type1; Gruber syndrome; MKS; Mes; Meckel-Gruber syndrome; Meckel Gruber syndrome; Dysencephalia splachnocystica; Meckel syndrome 1; MKS1 Meckel syndrome; MKS1; Meckel syndrome caused by mutation in MKS1; Meckel-Gruber syndrome, type 1; Meckel syndrome, type 1

Definition

Any Meckel syndrome in which the cause of the disease is a mutation in the MKS1 gene.

Disease Hierarchy

DISFLSDF: Polydactyly-syndactyly-triphalangism

DISXPHOY: Meckel syndrome

DIS4YWZU: Meckel syndrome, type 1

Disease Identifiers

MONDO ID

MONDO_0009571

MESH ID

C536133

UMLS CUI

C3714506

OMIM ID

249000

MedGen ID

811346

General Information of Disease (ID: DIS4YWZU)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
TRIM37	TTAMCSL	Limited	Genetic Variation	[1]
CEP290	TT3XBOV	Strong	Genetic Variation	[2]
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This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
LPO	DEHX1DZ	Strong	Genetic Variation	[3]
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This Disease Is Related to 22 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ALDH1A3	OT1C9NKQ	Limited	Biomarker	[4]
B9D1	OTWTXO75	Limited	Genetic Variation	[5]
BBS4	OT0D3JC0	Limited	Biomarker	[6]
CSPP1	OTNX7GD4	Limited	Biomarker	[7]
DVL1	OTD67RF1	Limited	Altered Expression	[8]
IFT140	OT6KO5FH	Limited	Biomarker	[9]
NPHP1	OTZHCFFQ	Limited	Genetic Variation	[10]
RPGRIP1	OTABESO9	Limited	Genetic Variation	[11]
SEPTIN4	OTD16B30	Limited	Biomarker	[12]
TMEM107	OT9RMLBJ	moderate	Biomarker	[13]
ARL13A	OT979K7Z	Strong	Biomarker	[14]
CC2D2A	OTFGRGFR	Strong	Biomarker	[15]
CEP120	OT1ZMRHL	Strong	Biomarker	[16]
INPP5E	OTJF2AZ9	Strong	Genetic Variation	[17]
INVS	OT8KPESR	Strong	Genetic Variation	[14]
RPGRIP1L	OT6Z069I	Strong	Biomarker	[18]
TCTN1	OTG5KEV8	Strong	Genetic Variation	[19]
TCTN2	OTKR3I3L	Strong	Genetic Variation	[20]
TMEM216	OT1LOKOI	Strong	Biomarker	[21]
TMEM231	OTF4UYIE	Strong	Genetic Variation	[22]
TMEM67	OTME92T5	Strong	Genetic Variation	[23]
MKS1	OT83W5PB	Definitive	Autosomal recessive	[24]
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⏷ Show the Full List of 22 DOT(s)

References

1	High-resolution physical and genetic mapping of the critical region for Meckel syndrome and Mulibrey Nanism on chromosome 17q22-q23.Genome Res. 1999 Mar;9(3):267-76.
2	Whole exome sequencing identified a homozygous novel variant in CEP290 gene causes Meckel syndrome.J Cell Mol Med. 2020 Jan;24(2):1906-1916. doi: 10.1111/jcmm.14887. Epub 2019 Dec 15.
3	Spectrum of MKS1 and MKS3 mutations in Meckel syndrome: a genotype-phenotype correlation. Mutation in brief #960. Online. Hum Mutat. 2007 May;28(5):523-4. doi: 10.1002/humu.9489.
4	Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3.Proc Natl Acad Sci U S A. 2013 May 21;110(21):8644-9. doi: 10.1073/pnas.1221478110. Epub 2013 May 6.
5	Joubert syndrome: genotyping a Northern European patient cohort.Eur J Hum Genet. 2016 Feb;24(2):214-20. doi: 10.1038/ejhg.2015.84. Epub 2015 Apr 29.
6	The Meckel syndrome- associated protein MKS1 functionally interacts with components of the BBSome and IFT complexes to mediate ciliary trafficking and hedgehog signaling.PLoS One. 2017 Mar 14;12(3):e0173399. doi: 10.1371/journal.pone.0173399. eCollection 2017.
7	Mutations in CSPP1, encoding a core centrosomal protein, cause a range of ciliopathy phenotypes in humans.Am J Hum Genet. 2014 Jan 2;94(1):73-9. doi: 10.1016/j.ajhg.2013.11.010. Epub 2013 Dec 19.
8	Variable expressivity of ciliopathy neurological phenotypes that encompass Meckel-Gruber syndrome and Joubert syndrome is caused by complex de-regulated ciliogenesis, Shh and Wnt signalling defects.Hum Mol Genet. 2013 Apr 1;22(7):1358-72. doi: 10.1093/hmg/dds546. Epub 2013 Jan 2.
9	Intraflagellar Transport Complex A Genes Differentially Regulate Cilium Formation and Transition Zone Gating.Curr Biol. 2018 Oct 22;28(20):3279-3287.e2. doi: 10.1016/j.cub.2018.08.017. Epub 2018 Oct 4.
10	Novel transglutaminase-like peptidase and C2 domains elucidate the structure, biogenesis and evolution of the ciliary compartment.Cell Cycle. 2012 Oct 15;11(20):3861-75. doi: 10.4161/cc.22068. Epub 2012 Sep 14.
11	The ciliopathy-associated protein homologs RPGRIP1 and RPGRIP1L are linked to cilium integrity through interaction with Nek4 serine/threonine kinase.Hum Mol Genet. 2011 Sep 15;20(18):3592-605. doi: 10.1093/hmg/ddr280. Epub 2011 Jun 17.
12	Characterization of a novel gene, PNUTL2, on human chromosome 17q22-q23 and its exclusion as the Meckel syndrome gene.Genomics. 1999 Jan 1;55(1):122-5. doi: 10.1006/geno.1998.5612.
13	TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubertsyndrome.Nat Cell Biol. 2016 Jan;18(1):122-31. doi: 10.1038/ncb3273. Epub 2015 Nov 23.
14	Active transport and diffusion barriers restrict Joubert Syndrome-associated ARL13B/ARL-13 to an Inv-like ciliary membrane subdomain.PLoS Genet. 2013;9(12):e1003977. doi: 10.1371/journal.pgen.1003977. Epub 2013 Dec 5.
15	Mks6 mutations reveal tissue- and cell type-specific roles for the cilia transition zone.FASEB J. 2019 Jan;33(1):1440-1455. doi: 10.1096/fj.201801149R. Epub 2018 Aug 22.
16	Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes. J Med Genet. 2016 Sep;53(9):608-15. doi: 10.1136/jmedgenet-2016-103832. Epub 2016 May 6.
17	Phenotypic spectrum and prevalence of INPP5E mutations in Joubert syndrome and related disorders. Eur J Hum Genet. 2013 Oct;21(10):1074-8. doi: 10.1038/ejhg.2012.305. Epub 2013 Feb 6.
18	The role of primary cilia in corpus callosum formation is mediated by production of the Gli3 repressor.Hum Mol Genet. 2015 Sep 1;24(17):4997-5014. doi: 10.1093/hmg/ddv221. Epub 2015 Jun 12.
19	Expanding the allelic disorders linked to TCTN1 to include Varadi syndrome (Orofaciodigital syndrome type VI). Am J Med Genet A. 2017 Sep;173(9):2439-2441. doi: 10.1002/ajmg.a.38336. Epub 2017 Jun 20.
20	Super-Resolution Imaging Reveals TCTN2 Depletion-Induced IFT88 Lumen Leakage and CiliaryWeakening.Biophys J. 2018 Jul 17;115(2):263-275. doi: 10.1016/j.bpj.2018.04.051. Epub 2018 Jun 1.
21	Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation. Am J Hum Genet. 2010 Jan;86(1):93-7. doi: 10.1016/j.ajhg.2009.12.007. Epub 2009 Dec 31.
22	Long-read nanopore sequencing resolves a TMEM231 gene conversion event causing Meckel-Gruber syndrome.Hum Mutat. 2020 Feb;41(2):525-531. doi: 10.1002/humu.23940. Epub 2019 Nov 11.
23	Hydrocephalus in a rat model of Meckel Gruber syndrome with a TMEM67 mutation.Sci Rep. 2019 Jan 31;9(1):1069. doi: 10.1038/s41598-018-37620-5.
24	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.