Details of Disease

General Information of Disease (ID: DISW3OY8)

• Disease Name: Hypoplastic left heart syndrome 1
• Synonyms: HLHS1; HLHS; GJA1 hypoplastic left heart syndrome; hypoplastic left heart syndrome caused by mutation in GJA1; hypoplastic left heart syndrome 1; hypoplastic left heart syndrome type 1
• Definition: Any hypoplastic left heart syndrome in which the cause of the disease is a mutation in the GJA1 gene.
• Disease Hierarchy:
  DISSLFZ4: Hypoplastic left heart syndrome
  DISW3OY8: Hypoplastic left heart syndrome 1
• Disease Identifiers:
  MONDO ID: MONDO_0009433
  UMLS CUI: C4551854
  OMIM ID: 241550
  MedGen ID: 1646779

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ENSA	TTQD0YT	Limited	Genetic Variation	[1]
ADCY5	TTN64VU	Strong	Altered Expression	[2]
GJA1	TT4F7SL	Strong	Biomarker	[3]
PLN	TTMCVJF	Strong	Posttranslational Modification	[2]
TNNT2	TTWAS18	Strong	Altered Expression	[4]
GJA1	TT4F7SL	Definitive	Autosomal dominant	[5]

This Disease Is Related to 15 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
C16orf95	OT5FMWHV	Limited	Genetic Variation	[6]
MYH7B	OTCB2IJB	Limited	Genetic Variation	[1]
SAP130	OT01SO0E	Limited	Genetic Variation	[7]
SYNPR	OTNCJ9L0	Limited	Genetic Variation	[6]
NKX2-5	OTS1SAWM	moderate	Biomarker	[8]
CAMK2G	OTHD9KJG	Strong	Altered Expression	[2]
CAMK4	OT47RDGV	Strong	Altered Expression	[2]
HAND1	OTN4IPVV	Strong	Genetic Variation	[9]
MCTP2	OTFMZ8I2	Strong	Genetic Variation	[10]
MGAT4A	OT0ZW5FM	Strong	Genetic Variation	[11]
MYH6	OT3YNCH1	Strong	Genetic Variation	[12]
PKD1L2	OTVDFDED	Strong	Genetic Variation	[11]
RBFOX2	OTXY1WVH	Strong	Biomarker	[13]
GJA1	OTT94MKL	Definitive	Autosomal dominant	[5]
PCDHA13	OTINVKS2	Definitive	Genetic Variation	[14]

References

• [1] A genome-wide association study of congenital cardiovascular left-sided lesions shows association with a locus on chromosome 20.Hum Mol Genet. 2016 Jun 1;25(11):2331-2341. doi: 10.1093/hmg/ddw071. Epub 2016 Mar 9.
• [2] Gene expression and -adrenergic signaling are altered in hypoplastic left heart syndrome.J Heart Lung Transplant. 2014 Aug;33(8):785-93. doi: 10.1016/j.healun.2014.02.030. Epub 2014 Mar 5.
• [3] Oculodentodigital dysplasia: new ocular findings and a novel connexin 43 mutation.Arch Ophthalmol. 2011 Jun;129(6):781-4. doi: 10.1001/archophthalmol.2011.113.
• [4] Directed differentiation of patient-specific induced pluripotent stem cells identifies the transcriptional repression and epigenetic modification of NKX2-5, HAND1, and NOTCH1 in hypoplastic left heart syndrome.PLoS One. 2014 Jul 22;9(7):e102796. doi: 10.1371/journal.pone.0102796. eCollection 2014.
• [5] Identification of connexin43 (alpha1) gap junction gene mutations in patients with hypoplastic left heart syndrome by denaturing gradient gel electrophoresis (DGGE). Mutat Res. 2001 Aug 8;479(1-2):173-86. doi: 10.1016/s0027-5107(01)00160-9.
• [6] Genome-wide association study of maternal and inherited effects on left-sided cardiac malformations.Hum Mol Genet. 2015 Jan 1;24(1):265-73. doi: 10.1093/hmg/ddu420. Epub 2014 Aug 18.
• [7] The Genetic Landscape of Hypoplastic Left Heart Syndrome.Pediatr Cardiol. 2018 Aug;39(6):1069-1081. doi: 10.1007/s00246-018-1861-4. Epub 2018 Mar 22.
• [8] Re-evaluation of hypoplastic left heart syndrome from a developmental and morphological perspective.Orphanet J Rare Dis. 2017 Aug 10;12(1):138. doi: 10.1186/s13023-017-0683-4.
• [9] The HAND1 frameshift A126FS mutation does not cause hypoplastic left heart syndrome in mice.Cardiovasc Res. 2017 Dec 1;113(14):1732-1742. doi: 10.1093/cvr/cvx166.
• [10] MCTP2 is a dosage-sensitive gene required for cardiac outflow tract development.Hum Mol Genet. 2013 Nov 1;22(21):4339-48. doi: 10.1093/hmg/ddt283. Epub 2013 Jun 16.
• [11] Genome-Wide Association Studies and Meta-Analyses for Congenital Heart Defects.Circ Cardiovasc Genet. 2017 Jun;10(3):e001449. doi: 10.1161/CIRCGENETICS.116.001449.
• [12] Impact of MYH6 variants in hypoplastic left heart syndrome.Physiol Genomics. 2016 Dec 1;48(12):912-921. doi: 10.1152/physiolgenomics.00091.2016. Epub 2016 Oct 27.
• [13] Rbfox2 function in RNA metabolism is impaired in hypoplastic left heart syndrome patient hearts.Sci Rep. 2016 Aug 3;6:30896. doi: 10.1038/srep30896.
• [14] The complex genetics of hypoplastic left heart syndrome.Nat Genet. 2017 Jul;49(7):1152-1159. doi: 10.1038/ng.3870. Epub 2017 May 22.