A Familial Insulin-Like Growth Factor-I Receptor Mutant Leads to Short Stature: Clinical and Biochemical Characterization

Inagaki, Kenjiro; Tiulpakov, Anatoly; Rubtsov, P. M.; Sverdlova, P. S.; Peterkova, Valentina; Yakar, Shoshana; Терехов, С. Н.; LeRoith, Derek

doi:10.1210/jc.2006-2354

Cited by 95 publications

(89 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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%

See 3 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

show abstract

“…In support of this, 22 NS specific to single species of NWM and 5 NS specific to subsets of NWM were identified in GHSR, IGF2, IGF1R and IGFBP2 (Dataset S5). Numerous IGF1R mutations are associated with both late prenatal and early postnatal growth restriction in humans (62,63), and mutations of IGF1R in mice have been demonstrated to slow embryonic growth (64). IGF2 is the primary growth factor controlling placental development and growth and is also critical in early embryonic growth (65)(66)(67)(68).…”

Section: Discussionmentioning

confidence: 99%

Evolutionary genetics and implications of small size and twinning in callitrichine primates

Harris

Tardif

Vinař

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

New World monkeys (NWMs) are characterized by an extensive size range, with clawed NWMs (subfamily Callitrichinae, or callitrichines) such as the common marmoset manifesting diminutive size and unique reproductive adaptations. Perhaps the most notable of these adaptations is their propensity toward multiple gestations (i.e., dichorionic twins and trichorionic triplets). Indeed, with the exception of Goeldi's monkey (Callimico), callitrichine singleton pregnancies rarely occur. Multiple gestations seem to have coevolved with a suite of reproductive adaptations, including hematopoetic chimerism of siblings, suppression of reproduction in nondominant females, and cooperative alloparenting. The sequencing of the common marmoset (Callithrix jacchus) genome offers the opportunity to explore the genetic basis of these unusual traits within this primate lineage. In this study, we hypothesized that genetic changes arising during callitrichine evolution resulted in multiple ovulated ova with each cycle, and that these changes triggered adaptations that minimized complications common to multiple gestations in other primates, including humans. Callitrichine-specific nonsynonymous substitutions were identified in GDF9, BMP15, BMP4, and WFIKKN1. WFIKKN1, a multidomain protease inhibitor that binds growth factors and bone morphogenetic proteins, has nonsynonymous changes found exclusively in common marmosets and other tested callitrichine species that twin. In the one callitrichine species that does not produce twins (Callimico), this change has reverted back to the ancestral (nontwinning) primate sequence. Polymorphisms in GDF9 occur among human cohorts with a propensity for dizygotic twins, and polymorphisms in GDF9 and BMP15 are associated with twinning in sheep. We postulate that positive selection affected NWM growth patterns, with callitrichine miniaturization coevolving with a series of reproductive adaptations.reproductive biology | primate evolution

show abstract

Congenital Disorders of the Hypothalamo‐Pituitary‐Somatotrope Axis

Mehta¹,

Gevers

Dattani

2009

Brook's Clinical Pediatric Endocrinology

View full text Add to dashboard Cite

A Familial Insulin-Like Growth Factor-I Receptor Mutant Leads to Short Stature: Clinical and Biochemical Characterization

Cited by 95 publications

References 25 publications

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

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

Evolutionary genetics and implications of small size and twinning in callitrichine primates

Congenital Disorders of the Hypothalamo‐Pituitary‐Somatotrope Axis

Contact Info

Product

Resources

About