Details of Disease

General Information of Disease (ID: DISLPIAM)

• Disease Name: Isolated growth hormone deficiency type IA
• Synonyms: isolated Growth hormone deficiency, type 1A; Illig-type Growth hormone deficiency; IGHD1A; ILLIG type growth hormone deficiency; isolated growth hormone deficiency, type IA; IGHD 1A; Growth hormone deficiency, isolated, autosomal recessive; congenital IGHD; non-acquired isolated growth hormone deficiency; congenital isolated GH deficiency; pituitary dwarfism 1; congenital isolated growth hormone deficiency; Growth hormone deficiency, isolated autosomal recessive; isolated growth hormone deficiency type 1A; isolated growth hormone deficiency type IA; growth hormone deficiency, isolated, type IA; sexual ateleiotic dwarfism; congenital IGHD type IA; congenital isolated growth hormone deficiency type IA; pituitary dwarfism I; Illig-type growth hormone deficiency; congenital isolated GH deficiency type IA; primordial dwarfism; autosomal recessive isolated growth hormone deficiency; IGHD IA
• Definition: An isolated growth hormone deficiency characterized by autosomal recessive inheritance of severe dwarfism with onset by 6 months of age and variable development of antibodies to growth hormone following exogenous supplementation that has material basis in null mutations in the GH1 gene on chromosome 17q23.3.
• Disease Hierarchy:
  DISTL7RP: Isolated congenital growth hormone deficiency
  DISLPIAM: Isolated growth hormone deficiency type IA
• Disease Identifiers:
  MONDO ID: MONDO_0009876
  MESH ID: C537404
  UMLS CUI: C0342573
  OMIM ID: 262400
  MedGen ID: 90986
  Orphanet ID: 231662
  SNOMED CT ID: 71003000

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BRCA2	TTUARD6	moderate	Genetic Variation	[1]
GH1	TTT3YKH	Strong	GermlineCausalMutation	[2]
GMNN	TT390KA	Strong	Biomarker	[3]
GH1	TTT3YKH	Definitive	Autosomal recessive	[4]

This Disease Is Related to 14 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
RNPC3	OTW5MKC1	Supportive	Autosomal recessive	[5]
TRAIP	OTMPT9Y2	moderate	Genetic Variation	[6]
CDT1	OTVY53VG	Strong	Genetic Variation	[7]
CENPJ	OTZCQZN5	Strong	Genetic Variation	[8]
GHRH	OT94U6MO	Strong	Biomarker	[9]
KATNB1	OT7CLZKS	Strong	Biomarker	[10]
LARP7	OTLLOZTL	Strong	Biomarker	[11]
NSMCE2	OTJXLDC9	Strong	Biomarker	[12]
ORC1	OTHWU8IJ	Strong	Biomarker	[13]
PCNT	OTW4Z65J	Strong	Genetic Variation	[8]
RTTN	OT5PB986	Strong	Genetic Variation	[14]
CRIPT	OTA6M8M4	Definitive	Genetic Variation	[15]
GH1	OT92RTRD	Definitive	Autosomal recessive	[4]
LIG4	OT40DNXU	Definitive	CausalMutation	[16]

References

• [1] Genomic analysis of primordial dwarfism reveals novel disease genes. Genome Res. 2014 Feb;24(2):291-9. doi: 10.1101/gr.160572.113. Epub 2014 Jan 3.
• [2] Phenotype-genotype correlations in congenital isolated growth hormone deficiency (IGHD).Indian J Pediatr. 2012 Jan;79(1):99-106. doi: 10.1007/s12098-011-0614-7. Epub 2011 Dec 3.
• [3] De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome. Am J Hum Genet. 2015 Dec 3;97(6):904-13. doi: 10.1016/j.ajhg.2015.11.006.
• [4] 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.
• [5] Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency. EMBO Mol Med. 2014 Mar;6(3):299-306. doi: 10.1002/emmm.201303573. Epub 2014 Jan 30.
• [6] TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism. Nat Genet. 2016 Jan;48(1):36-43. doi: 10.1038/ng.3451. Epub 2015 Nov 23.
• [7] Cdt1 variants reveal unanticipated aspects of interactions with cyclin/CDK and MCM important for normal genome replication.Mol Biol Cell. 2018 Dec 1;29(25):2989-3002. doi: 10.1091/mbc.E18-04-0242. Epub 2018 Oct 3.
• [8] Novel CENPJ mutation causes Seckel syndrome. J Med Genet. 2010 Jun;47(6):411-4. doi: 10.1136/jmg.2009.076646.
• [9] GH, but not GHRH, plays a role in the development of experimental autoimmune encephalomyelitis.Endocrinology. 2011 Oct;152(10):3803-10. doi: 10.1210/en.2011-1317. Epub 2011 Aug 16.
• [10] A syndrome of microcephaly, short stature, polysyndactyly, and dental anomalies caused by a homozygous KATNB1 mutation.Am J Med Genet A. 2016 Mar;170(3):728-33. doi: 10.1002/ajmg.a.37484. Epub 2015 Dec 6.
• [11] Compound heterozygous variants in the LARP7 gene as a cause of Alazami syndrome in a Caucasian female with significant failure to thrive, short stature, and developmental disability.Am J Med Genet A. 2016 Jan;170A(1):217-9. doi: 10.1002/ajmg.a.37396. Epub 2015 Sep 16.
• [12] Hypomorphism in human NSMCE2 linked to primordial dwarfism and insulin resistance. J Clin Invest. 2014 Sep;124(9):4028-38. doi: 10.1172/JCI73264. Epub 2014 Aug 8.
• [13] The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome.Nature. 2012 Mar 7;484(7392):115-9. doi: 10.1038/nature10956.
• [14] A neuropathological study of novel RTTN gene mutations causing a familial microcephaly with simplified gyral pattern.Birth Defects Res. 2018 Apr 17;110(7):598-602. doi: 10.1002/bdr2.1204. Epub 2018 Jan 22.
• [15] CRIPT exonic deletion and a novel missense mutation in a female with short stature, dysmorphic features, microcephaly, and pigmentary abnormalities.Am J Med Genet A. 2016 Aug;170(8):2206-11. doi: 10.1002/ajmg.a.37780. Epub 2016 Jun 2.
• [16] Extreme growth failure is a common presentation of ligase IV deficiency.Hum Mutat. 2014 Jan;35(1):76-85. doi: 10.1002/humu.22461. Epub 2013 Nov 8.