RGD Reference Report - Short stature associated with a novel heterozygous mutation in the insulin-like growth factor 1 gene. - Rat Genome Database

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Short stature associated with a novel heterozygous mutation in the insulin-like growth factor 1 gene.

Authors: Van Duyvenvoorde, HA  Van Setten, PA  Walenkamp, MJ  Van Doorn, J  Koenig, J  Gauguin, L  Oostdijk, W  Ruivenkamp, CA  Losekoot, M  Wade, JD  De Meyts, P  Karperien, M  Noordam, C  Wit, JM 
Citation: van Duyvenvoorde HA, etal., J Clin Endocrinol Metab. 2010 Nov;95(11):E363-7. doi: 10.1210/jc.2010-0511. Epub 2010 Jul 28.
RGD ID: 8548823
Pubmed: PMID:20668042   (View Abstract at PubMed)
DOI: DOI:10.1210/jc.2010-0511   (Journal Full-text)

CONTEXT: Homozygous IGF1 deletions or mutations lead to severe short stature, deafness, microcephaly, and mental retardation. Heterozygosity for an IGF-I defect may modestly decrease height and head circumference. OBJECTIVE: The objective of the study was to investigate the clinical features of heterozygous carriers of a novel mutation in the IGF1 gene in comparison with noncarriers in a short family and to establish the effect of human GH treatment. SUBJECTS: Two children, their mother, and their maternal grandfather carried the mutation and were compared with two relatives who were noncarriers. RESULTS: The two index cases had severe short stature (height sd score -4.1 and -4.6), microcephaly, and low IGF-I levels. Sequencing of IGF1 revealed a heterozygous duplication of four nucleotides, resulting in a frame shift and a premature termination codon. The mother and maternal grandfather had the same IGF1 mutation. Adult height (corrected for shrinking and secular trend) and head circumference sd score of carriers of the paternally transmitted mutation was -2.5 and -1.8, in comparison with -1.6 and 0.3 in noncarriers, respectively. After 2 yr of GH treatment, both index cases exhibited increased growth. CONCLUSIONS: Heterozygosity for this novel IGF1 mutation in children born from a mother with the same mutation, presumably in combination with other genetic factors for short stature, leads to severe short stature, which can be successfully treated with GH.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Dwarfism  IMP 8548823DNA:nonsense mutation and haploinsufficiency :cds:RGD 
Dwarfism  ISOIGF1 (Homo sapiens)8548823; 8548823DNA:nonsense mutation and haploinsufficiency :cds:RGD 
microcephaly  IMP 8548823DNA:nonsense mutation and haploinsufficiency :cds:RGD 
microcephaly  ISOIGF1 (Homo sapiens)8548823; 8548823DNA:nonsense mutation and haploinsufficiency :cds:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Igf1  (insulin-like growth factor 1)

Genes (Mus musculus)
Igf1  (insulin-like growth factor 1)

Genes (Homo sapiens)
IGF1  (insulin like growth factor 1)


Additional Information