Response to Growth Hormone Treatment in a Patient with Insulin-Like Growth Factor 1 Receptor Deletion

Mahmoud, Ranim; Naidu, Ajanta; Risheg, Hiba; Kimonis, Virginia

doi:10.4274/jcrpe.4456

Cited by 8 publications

(10 citation statements)

References 23 publications

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“…Also the c.1549A > T, the p.Y487F mutation was reported in a patient with microcephaly and prenatal and postnatal growth impairment [ 24 ]. GH treatment of a patient with short stature, microcephaly, dysmorphic features, developmental delay and a terminal deletion of 15q26.2q26.3 containing the IGF1R gene in addition to a terminal duplication of the 4q35.1q35.2 region resulted in a strong growth response [ 25 ]. It is of note that the GH treatment in our patients had mixed effects.…”

Section: Discussionmentioning

confidence: 99%

IGF1R Gene Alterations in Children Born Small for Gestitional Age (SGA)

Janchevska¹,

Krstevska-Konstantinova²,

Pfäffle³

et al. 2018

Open Access Maced J Med Sci

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BACKGROUND:Small for gestational age (SGA)-born children are a heterogeneous group with few genetic causes reported. Genetic alterations in the IGF1 receptor (IGF1R) are found in some SGA children.AIM:To investigate whether alterations in IGF1R gene are present in SGA born children.PATIENTS AND METHODS:We analysed 64 children born SGA who stayed short (mean -3.25 ± 0.9 SDS) within the first 4 years of age, and 36 SGA children who caught up growth (0.20 ± 1.1 SDS). PCR products of all coding IGF1R exons were screened by dHPLC followed by direct sequencing of conspicuous fragments to identify small nucleotide variants. The presence of IGF1R gene copy number alterations was determined by Multiplex Ligation-dependent Probe Amplification (MLPA).RESULTS:The cohort of short SGA born children revealed a heterozygous, synonymous variant c.3453C > T in one patient and a novel heterozygous 3 bp in-frame deletion (c.3234_3236delCAT) resulting in one amino acid deletion (p.Ile1078del) in another patient. The first patient had normal serum levels of IGF1. The second patient had unusually low IGF1 serum concentrations (-1.57 SD), which contrasts previously published data where IGF1 levels rarely are found below the age-adjusted mean.CONCLUSIONS:IGF1R gene alterations were present in 2 of 64 short SGA children. The patients did not have any dysmorphic features or developmental delay. It is remarkable that one of them had significantly decreased serum concentrations of IGF1. Growth response to GH treatment in one of the patients was favourable, while the second one discontinued the treatment, but with catch-up growth.

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Section: Discussionmentioning

confidence: 99%

IGF1R Gene Alterations in Children Born Small for Gestitional Age (SGA)

Janchevska¹,

Krstevska-Konstantinova²,

Pfäffle³

et al. 2018

Open Access Maced J Med Sci

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“…Several alterations (point mutations and deletions) in the IGF1 and insulin-like growth factor 1 receptor ( IGF-1R ) genes have been demonstrated last decade. Alterations have been identified that affect IGF1R biosynthesis, signal reception and receptor kinase activity [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

IGF1R Gene Alterations in Small for Gestational Age (SGA) Children

Janchevska¹,

Dimovski²,

Mironska³

et al. 2018

Open Access Maced J Med Sci

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BACKGROUND:Small for gestational age children (SGA) is born on term with BW and or BL of -2.0 standard deviation score (SDS). SGA children have an increased risk of being short, developing DM, and cardiovascular and cerebrovascular disease. Often defects of IGF1R are the cause of SGA. Most frequently affected part of the IGF1R gene is the exon 2.AIM:To investigate whether the exon 2 of the IGF1R gene is affected in the SGA children.PATIENTS AND METHODS:A cohort of 100 SGA children born in term was evaluated for alterations in IG1R gene. Their anthropometric parameters, IGF1 serum concentrations and IGF1 SDS values were analysed. The molecular analysis of IGF1R gene was performed by PCR restriction-site analysis and followed by direct sequencing of conspicuous fragments.RESULTS:Within our cohort, 64 SGA children were with short stature (height SDS -3.25 ± 0.90 SDS), and 36 were with normal height for their age and sex, (H SDS was 0.20 ± 1.1 SDS). None of these children had microcephaly (occipitofrontal circumference -0.70 ± 1.01 SDS vs 0.06 ± 0.56 SDS in SGA children with normal height) or dysmorphic features. The IGF1 serum concentrations and IGF1 SDS values of all children were within normal range. Only one child had lower normal serum IGF1 concentration. No alterations in exon 2 of IGF1R gene were detected.CONCLUSIONS:The genetic analysis of the exon 2 of the IGF1R gene did not detect any gene defects in the analysed patients. The putative genetic defect in those children affects other parts of the IGF1R gene or another gene (s), or yet unidentified factors.

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“…Moreover, the response to conventional growth hormone (GH) therapy in patients with IGF-1R and IGF-1 mutations is notably variable (8). While some patients demonstrate a good growth response (8)(9)(10), others show little to no improvement (11,12).…”

Section: Introductionmentioning

confidence: 99%

Insight into Insulin-like Growth Factor-1 Receptor (IGF-1R) gene mutations: Implications for growth disorders and treatment: A review of the literature and case report

Ashraf Soliman,

Fawzia Alyafei,

Vincenzo De Sanctis

et al. 2024

World J. Adv. Res. Rev.

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Background: Insulin-like Growth Factor -1 Receptor (IGF-1R) and its ligand, IGF-1, are crucial for human tissue growth and development. Mutations in IGF-1R and, to a lesser extent, IGF-1 genes lead to diverse growth disorders, characterized by intrauterine growth retardation and postnatal growth challenges. Case report: We present a case of a 6-year-old girl with speech and mild cognitive delays, exhibiting normal motor skills, no neurological issues, and standard vital signs. Her growth parameters indicated significant retardation, with a height standard deviation score (Ht-SDS) of -2 and an IGF-1 level of +1.8 SDS, normal thyroid function and delayed bone age. Genetic analysis identified a 3335 mbp interstitial loss in 15q26.1, encompassing the IGF-1R gene, critical for growth and development. Literature review: Analysis of 34 papers provided insight into the genetic complexities of IGF-1R and IGF-1 mutations. Studies ranged from familial cases to cohort studies, uncovering mutations including missense mutations, deletions, and copy number variations (CNVs), each associated with unique growth disorder phenotypes. Advances in diagnostic techniques like multiplex ligation-dependent probe amplification (MLPA) and whole exome sequencing (WES) have been pivotal in identifying these mutations, facilitating more targeted management approaches. Conclusions: This case and review of literature underscore the importance of an integrated genetic, endocrine, and developmental approach in managing growth hormone deficiency (GHD) and IGF-1 resistance. The variability in growth disorders and response to therapy highlights the need for personalized treatment plans, informed by genetic insights, to optimize outcomes for patients with these complex conditions.

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Response to Growth Hormone Treatment in a Patient with Insulin-Like Growth Factor 1 Receptor Deletion

Cited by 8 publications

References 23 publications

IGF1R Gene Alterations in Children Born Small for Gestitional Age (SGA)

IGF1R Gene Alterations in Children Born Small for Gestitional Age (SGA)

IGF1R Gene Alterations in Small for Gestational Age (SGA) Children

Insight into Insulin-like Growth Factor-1 Receptor (IGF-1R) gene mutations: Implications for growth disorders and treatment: A review of the literature and case report

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