Proportional growth failure and oculocutaneous albinism in a girl with a 6.87 Mb deletion of region 15q26.2→qter

Poot, Martin; Eleveld, Marc J.; Slot, Ruben van ‘t; Genderen, Maria M. van; Stuart, A. A. Verrijn; Hochstenbach, Ron; Beemer, Frits A.

doi:10.1016/j.ejmg.2007.08.003

Cited by 44 publications

(43 citation statements)

References 17 publications

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“…Moreover, our patient was born with a cardiac defect -a finding that is frequently observed in carriers of heterozygous 15q26 deletions (including the IGF1R locus) but has been ascribed to genes located proximally to the IGF1R gene (22). However, SNP array analysis in our patient did not show any pathogenic CNV and, thus, the cause of the heart defect remains elusive.…”

Section: Discussionmentioning

confidence: 66%

“…Mutations in the IGF1R gene in the heterozygous state have been recently described as a cause of IUGR (7) and lead to partial resistance to IGF1 and contribute to IUGR with postnatal growth failure, microcephaly, and normal or increased levels of serum IGF1 and IGF binding protein 3 (IGFBP3), sometimes associated with modestly impaired intellectual development (8,9,10,11,12,13,14,15,16,17,18,19,20,21). Skeletal and cardiac abnormalities might also be mainly present in patients with terminal deletion of chromosome 15q including the IGF1R locus (22), but these conditions are possibly caused by deletion of other genes. So far, only two patients were described with a compound heterozygous mutation in the IGF1R gene (8,20) while mutations in the homozygous state have never been reported.…”

Section: Introductionmentioning

confidence: 99%

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Homozygous mutation of the IGF1 receptor gene in a patient with severe pre- and postnatal growth failure and congenital malformations

Gannagé‐Yared

Klammt²,

Chouery

et al. 2013

European Journal of Endocrinology

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Background: Heterozygous mutations in the IGF1 receptor (IGF1R) gene lead to partial resistance to IGF1 and contribute to intrauterine growth retardation (IUGR) with postnatal growth failure. To date, homozygous mutations of this receptor have not been described. Subject: A 13.5-year-old girl born from healthy first-cousin parents presented with severe IUGR and persistent short stature. Mild intellectual impairment, dysmorphic features, acanthosis nigricans, and cardiac malformations were also present. Methods: Auxological and endocrinological profiles were measured. All coding regions of the IGF1R gene including intron boundaries were amplified and directly sequenced. Functional characterization was performed by immunoblotting using patient's fibroblasts. Results: IGF1 level was elevated at 950 ng/ml (C7 S.D.). Fasting glucose level was normal associated with high insulin levels at baseline and during an oral glucose tolerance test. Fasting triglyceride levels were elevated. Sequencing of the IGF1R gene led to the identification of a homozygous variation in exon 2: c.119GOT (p.Arg10Leu). As a consequence, IGF1-dependent receptor autophosphorylation and downstream signaling were reduced in patient's fibroblasts. Both parents were heterozygous for the mutation. Conclusion: The homozygous mutation of the IGF1R is associated with severe IUGR, dysmorphic features, and insulin resistance, while both parents were asymptomatic heterozygous carriers of the same mutation.

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Homozygous mutation of the IGF1 receptor gene in a patient with severe pre- and postnatal growth failure and congenital malformations

Gannagé‐Yared

Klammt²,

Chouery

et al. 2013

European Journal of Endocrinology

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“…Several of these cases have been described in detail. [39][40][41][42][43][44] In addition, we found nine inherited segmental aneuploidies. The 20 de novo aberrations encompassed 125 BAC probes, 14 of which were also identified as single CNCs shared among at least 2 other patients and 5 among the 48 healthy individuals of our study population.…”

Section: Resultsmentioning

confidence: 82%

Recurrent copy number changes in mentally retarded children harbour genes involved in cellular localization and the glutamate receptor complex

et al. 2009

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confidence: 99%

“…In this regard, haploinsufficiency of the gene for insulin-like growth factor 1 receptor (IGF1R) at 15q26.3 is known to be relevant to the growth failure and mental retardation [2], and hemizygosity of the gene for nuclear receptor subfamily group F member 2 (NR2F2) at 15q26.2 has been postulated as an underlying factor for CHD [3][4][5][6].The chromosome end is associated with 3-20 kb of tandemly repeated telomere sequences (TTAGGG) n that are extended and maintained in human germline by telomerase using an integral telomere-complementary RNA template [7][8][9]. The telomere sequences are essential for chromosome stability and DNA replica- abstract.…”

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confidence: 99%

Identification of chromosome 15q26 terminal deletion with telomere sequences and its bearing on genotype-phenotype analysis

et al. 2011

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Terminal deletions of chromosome 15q are relatively rare chromosomal anomalies that are usually associated with variable degrees of pre-and post-natal growth failure and are sometimes accompanied by mental retardation and/or congenital anomalies such as congenital heart defect (CHD) [1]. In this regard, haploinsufficiency of the gene for insulin-like growth factor 1 receptor (IGF1R) at 15q26.3 is known to be relevant to the growth failure and mental retardation [2], and hemizygosity of the gene for nuclear receptor subfamily group F member 2 (NR2F2) at 15q26.2 has been postulated as an underlying factor for CHD [3][4][5][6].The chromosome end is associated with 3-20 kb of tandemly repeated telomere sequences (TTAGGG) n that are extended and maintained in human germline by telomerase using an integral telomere-complementary RNA template [7][8][9]. The telomere sequences are essential for chromosome stability and DNA replica- abstract. We report a de novo heterozygous 5,013,940 bp terminal deletion of chromosome 15q26 in a 13 9/12 -year-old Japanese girl with short stature (-3.9 SD), mild mental retardation, and ventricular septal defect (VSD). This terminal deletion involved IGF1R but not NR2F2, and was associated with an addition of telomere repeat sequences (TTAGGG) at the end of the truncated chromosome. The results provide further support for the notion that terminal deletions are healed by de novo addition of telomere sequences essential for chromosome stability and DNA replication. Furthermore, while growth failure and mental retardation are primarily explained by loss of IGF1R, the occurrence of VSD might suggest the existence of a cardiac anomaly gene, other than the candidate cardiac anomaly gene NR2F2, in the deleted region.

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Proportional growth failure and oculocutaneous albinism in a girl with a 6.87 Mb deletion of region 15q26.2→qter

Cited by 44 publications

References 17 publications

Homozygous mutation of the IGF1 receptor gene in a patient with severe pre- and postnatal growth failure and congenital malformations

Homozygous mutation of the IGF1 receptor gene in a patient with severe pre- and postnatal growth failure and congenital malformations

Recurrent copy number changes in mentally retarded children harbour genes involved in cellular localization and the glutamate receptor complex

Identification of chromosome 15q26 terminal deletion with telomere sequences and its bearing on genotype-phenotype analysis

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