NM_001111284.1(IGF1):c.226G>A (p.Val76Met) AND Insulin-like growth factor I deficiency

Clinical significance:Pathogenic (Last evaluated: May 1, 2005)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000015912.27

Allele description [Variation Report for NM_001111284.1(IGF1):c.226G>A (p.Val76Met)]

NM_001111284.1(IGF1):c.226G>A (p.Val76Met)

Gene:
IGF1:insulin like growth factor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q23.2
Genomic location:
Preferred name:
NM_001111284.1(IGF1):c.226G>A (p.Val76Met)
HGVS:
  • NC_000012.12:g.102419637C>T
  • NG_011713.1:g.65964G>A
  • NM_000618.4:c.274G>A
  • NM_001111283.2:c.274G>A
  • NM_001111284.1:c.226G>A
  • NP_000609.1:p.Val92Met
  • NP_001104753.1:p.Val92Met
  • NP_001104754.1:p.Val76Met
  • NC_000012.11:g.102813415C>T
  • NM_000618.3:c.274G>A
  • NM_001111283.1:c.274G>A
Protein change:
V44M; VAL44MET
Links:
OMIM: 147440.0003; dbSNP: rs121912430
NCBI 1000 Genomes Browser:
rs121912430
Molecular consequence:
  • NM_001111283.2:c.274G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Insulin-like growth factor I deficiency
Identifiers:
MedGen: C1837475; Orphanet: 73272; OMIM: 608747

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000036179OMIMno assertion criteria providedPathogenic
(May 1, 2005)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Homozygous and heterozygous expression of a novel insulin-like growth factor-I mutation.

Walenkamp MJ, Karperien M, Pereira AM, Hilhorst-Hofstee Y, van Doorn J, Chen JW, Mohan S, Denley A, Forbes B, van Duyvenvoorde HA, van Thiel SW, Sluimers CA, Bax JJ, de Laat JA, Breuning MB, Romijn JA, Wit JM.

J Clin Endocrinol Metab. 2005 May;90(5):2855-64. Epub 2005 Mar 15.

PubMed [citation]
PMID:
15769976

Details of each submission

From OMIM, SCV000036179.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 55-year-old male with insulin-like growth factor I deficiency (608747), the first child of consanguineous parents, Walenkamp et al. (2005) found a homozygous G-to-A transition in the IGF1 gene changing valine-44 to methionine (V44M). Functional analysis demonstrating 90-fold reduced affinity of the mutant IGF1 for the IGF1 receptor proved the inactivating nature of the mutation. The phenotype included severe intrauterine growth retardation, deafness, and mental retardation, reflecting the GH-independent secretion of IGF1 in utero. Additional investigations revealed osteoporosis, a partial gonadal dysfunction, and a relatively well-preserved cardiac function. The postnatal growth pattern, similar to growth of untreated GH-deficient or GH-insensitive children, agrees with the hypothesis that IGF1 secretion in childhood is mainly GH-dependent. IGF1 haploinsufficiency results in subtle inhibition of intrauterine and postnatal growth.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 21, 2018