Details of Disease

General Information of Disease (ID: DISXPHOY)

• Disease Name: Meckel syndrome
• Synonyms: Meckel-Gruber syndrome
• Definition: A rare, lethal, genetic, multiple congenital anomaly disorder characterized by the triad of brain malformation mainly occipital encephalocele, large polycystic kidneys, and polydactyly as well as associated abnormalities that may include cleft lip/palate, cardiac and genital anomalies, central nervous system (CNS) malformations, liver fibrosis, and bone dysplasia.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DIS10G4I: Ciliopathy
  DISOGTFT: Hereditary lethal multiple congenital anomalies/dysmorphic syndrome
  DISXPHOY: Meckel syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0018921
  UMLS CUI: C0265215
  MedGen ID: 120513
  Orphanet ID: 564
  SNOMED CT ID: 29076005

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 17 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
TXNDC15	OTYOSAKM	Moderate	Autosomal recessive	[1]
CEP55	OTGSG2PA	Limited	GermlineCausalMutation	[5]
B9D1	OTWTXO75	Supportive	Autosomal recessive	[6]
B9D2	OT5SS4P8	Supportive	Autosomal recessive	[7]
CC2D2A	OTFGRGFR	Supportive	Autosomal recessive	[3]
CEP290	OTVN52VH	Supportive	Autosomal recessive	[3]
CSPP1	OTNX7GD4	Supportive	Autosomal recessive	[8]
MKS1	OT83W5PB	Supportive	Autosomal recessive	[3]
RPGRIP1L	OT6Z069I	Supportive	Autosomal recessive	[3]
TCTN1	OTG5KEV8	Supportive	Autosomal recessive	[9]
TCTN2	OTKR3I3L	Supportive	Autosomal recessive	[10]
TCTN3	OTZSHERV	Supportive	Autosomal recessive	[11]
TMEM107	OT9RMLBJ	Supportive	Autosomal recessive	[12]
TMEM216	OT1LOKOI	Supportive	Autosomal recessive	[3]
TMEM231	OTF4UYIE	Supportive	Autosomal recessive	[13]
TMEM237	OTQEVL7L	Supportive	Autosomal recessive	[14]
TMEM67	OTME92T5	Supportive	Autosomal recessive	[3]

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CEP290	TT3XBOV	Limited	Genetic Variation	[2]
CEP290	TT3XBOV	Supportive	Autosomal recessive	[3]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
LPO	DEHX1DZ	Strong	Genetic Variation	[4]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Ciliary genes arl13b, ahi1 and cc2d2a differentially modify expression of visual acuity phenotypes but do not enhance retinal degeneration due to mutation of cep290 in zebrafish.PLoS One. 2019 Apr 10;14(4):e0213960. doi: 10.1371/journal.pone.0213960. eCollection 2019.
• [3] Molecular genetics and pathogenic mechanisms for the severe ciliopathies: insights into neurodevelopment and pathogenesis of neural tube defects. Mol Neurobiol. 2011 Feb;43(1):12-26. doi: 10.1007/s12035-010-8154-0. Epub 2010 Nov 27.
• [4] 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.
• [5] A nonsense mutation in CEP55 defines a new locus for a Meckel-like syndrome, an autosomal recessive lethal fetal ciliopathy.Clin Genet. 2017 Nov;92(5):510-516. doi: 10.1111/cge.13012. Epub 2017 May 3.
• [6] B9D1 is revealed as a novel Meckel syndrome (MKS) gene by targeted exon-enriched next-generation sequencing and deletion analysis. Hum Mol Genet. 2011 Jul 1;20(13):2524-34. doi: 10.1093/hmg/ddr151. Epub 2011 Apr 14.
• [7] Disruption of a ciliary B9 protein complex causes Meckel syndrome. Am J Hum Genet. 2011 Jul 15;89(1):94-110. doi: 10.1016/j.ajhg.2011.06.003.
• [8] Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
• [9] 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.
• [10] A TCTN2 mutation defines a novel Meckel Gruber syndrome locus. Hum Mutat. 2011 Jun;32(6):573-8. doi: 10.1002/humu.21507. Epub 2011 May 5.
• [11] TCTN3 mutations cause Mohr-Majewski syndrome. Am J Hum Genet. 2012 Aug 10;91(2):372-8. doi: 10.1016/j.ajhg.2012.06.017.
• [12] Identification of a novel MKS locus defined by TMEM107 mutation. Hum Mol Genet. 2015 Sep 15;24(18):5211-8. doi: 10.1093/hmg/ddv242. Epub 2015 Jun 29.
• [13] Mutations in TMEM231 cause Meckel-Gruber syndrome. J Med Genet. 2013 Mar;50(3):160-2. doi: 10.1136/jmedgenet-2012-101431. Epub 2013 Jan 24.
• [14] Enhanced diagnostic yield in Meckel-Gruber and Joubert syndrome through exome sequencing supplemented with split-read mapping. BMC Med Genet. 2016 Jan 4;17:1. doi: 10.1186/s12881-015-0265-z.