Clinical and Functional Characteristics of the Human Arg59Ter Insulin-Like Growth Factor I Receptor (IGF1R) Mutation: Implications for a Gene Dosage Effect of the Human IGF1R

Raile, Klemens; Klammt, J; Schneider, Anke; Keller, Annika; Laue, S.; Smith, Rosemarie; Pfäffle, Roland; Kratzsch, Jürgen; Keller, E; Kieß, Wieland

doi:10.1210/jc.2005-2146

Cited by 75 publications

(78 citation statements)

References 33 publications

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“…Finally, therapeutic options can be discussed. It has been reported that GH therapy in patients with a heterozygous IGF1R mutation or deletion improves growth and head circumference (18,30,109,130). In the late 1980s, trials with rhIGF-I started in patients with GHR defects.…”

Section: Implications For the Patientmentioning

confidence: 99%

Genetic disorders in the GH–IGF-I axis in mouse and man

Walenkamp

Wit²

2007

eur j endocrinol

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Animal knockout experiments have offered the opportunity to study genes that play a role in growth and development. In the last few years, reports of patients with genetic defects in GH-IGF-I axis have greatly increased our knowledge of genetically determined causes of short stature. We will present the animal data and human reports of genetic disorders in the GH-IGF-I axis in order to describe the role of the GH-IGF-I axis in intrauterine and postnatal growth. In addition, the effects of the GH-IGF-I axis on the development and function of different organ systems such as brain, inner ear, eye, skeleton, glucose homeostasis, gonadal function, and immune system will be discussed. The number of patients with genetic defects in the GH-IGF-I axis is small, and a systematic diagnostic approach and selective genetic analysis in a patient with short stature are essential to identify more patients. Finally, the implications of a genetic defect in the GH-IGF-I axis for the patient and the therapeutic options will be discussed.European Journal of Endocrinology 157 S15-S26

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Section: Implications For the Patientmentioning

confidence: 99%

Genetic disorders in the GH–IGF-I axis in mouse and man

Walenkamp

Wit²

2007

eur j endocrinol

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“…These were located in exons 2, 7, 11 and 16, respectively. [1][2][3][4][5] Short stature was present in all cases, mild motor and/or speech developmental delay in 4/9 cases and mild intellectual disabilitywith a Wechsler intelligence quotient of 60 -in one case of a patient with a missense mutation in exon 11. This missense mutation was detected in a girl whose mother, a carrier of the same mutation, did not show any neuropsychiatric abnormalities and had normal intelligence.…”

Section: Discussionmentioning

confidence: 93%

“…They were associated with various constellations of clinical findings, including growth deficit, microcephaly, developmental delay, mild facial dysmorphisms and skeletal deformations in affected individuals. [1][2][3][4][5][6][7][8][9][10][11] Usually intrauterine or postnatal growth deficits were moderate to severe in these patients. Notably, cognitive dysfunction of the reported individuals was either moderate, mild or absent.…”

Section: Introductionmentioning

confidence: 79%

“…Missense and nonsense mutations in IGF1R segregated with short stature, mild dysmorphic facial features, mostly mild developmental delay and mild psychiatric features in one reported case. [1][2][3][4][5] Although the variable phenotype of previously reported patients with 15q26.3 deletions may be attributable, at least in part, to genes other than IGF1R, it is notable that the smallest IGF1R deletion reported to date segregated predominantly with short stature and no or mild neuropsychiatric disorders. 10 In that family described by Veenma et al, seven family members carried a deletion of exons 11-21 of the IGF1R gene and what at the time of publication used to be a hypothetical protein-locus (LOC145814), and is now annotated as a RefSeq gene, PGPEP1L, encoding pyroglutamyl-peptidase-I-like.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, cognitive dysfunction of the reported individuals was either moderate, mild or absent. [2][3][4] Significant psychiatric comorbidites beyond cognitive impairment have not been reported to date.…”

Section: Introductionmentioning

confidence: 99%

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Intragenic deletions of the IGF1 receptor gene in five individuals with psychiatric phenotypes and developmental delay

Witsch

Szafrański

Immken³

et al. 2013

Eur J Hum Genet

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Haploinsufficiency of the gene encoding the insulin-like growth factor 1 receptor (IGF1R), either caused by telomeric 15q26 deletions, or by heterozygous point mutations in IGF1R, segregate with short stature and various other phenotypes, including microcephaly and dysmorphic facial features. Psychomotor retardation and behavioral anomalies have been seen in some cases. Here we report small, intragenic deletions of IGF1R, identified by chromosome microarray analysis in two unrelated families affected primarily with neuropsychiatric phenotypes including developmental delay, intellectual disability and aggressive/ autoaggressive behaviors. The deletions are in frame, and both wild-type and mutant mRNAs are expressed as measured by quantitative real-time PCR. While short stature is considered a phenotypic hallmark of IGF1R haploinsufficiency, the present report suggests that in frame exon deletions of IGF1R present predominantly with cognitive and neuropsychiatric phenotypes.

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