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FGFR3 gene mutation plus GRB10 gene duplication in a patient with achondroplasia plus growth delay with prenatal onset.

Yuan H, Huang L, Hu X, Li Q, Sun X, Xie Y, Kong S, Wang X - Orphanet J Rare Dis (2016)

Bottom Line: Genotype- and phenotype-level correlations have been found between the clinical symptoms of achondroplasia and achondroplasia-specific FGFR3 mutations.Using quantitative real-time PCR analysis, GRB10 was over-expressed, and, using enzyme-linked immunosorbent assays for IGF1 and IGF-binding protein-3 (IGFBP3), we found that IGF1 and IGFBP3 were low-expressed in this patient.We demonstrate that a combination of uncommon, rare and exceptional molecular defects related to the molecular bases of particular birth defects can be analyzed and diagnosed to potentially explain the observed variability in the combination of molecular defects.

View Article: PubMed Central - PubMed

Affiliation: Guangzhou KingMed Center for Clinical Laboratory Co., Ltd, Guangzhou, 510330, Guangdong, China.

ABSTRACT

Background: Achondroplasia is a well-defined and common bone dysplasia. Genotype- and phenotype-level correlations have been found between the clinical symptoms of achondroplasia and achondroplasia-specific FGFR3 mutations.

Result: A 2-year-old boy with clinical features consistent with achondroplasia and Silver-Russell syndrome-like symptoms was found to carry a mutation in the fibroblast growth factor receptor-3 (FGFR3) gene at c.1138G > A (p.Gly380Arg) and a de novo 574 kb duplication at chromosome 7p12.1 that involved the entire growth-factor receptor bound protein 10 (GRB10) gene. Using quantitative real-time PCR analysis, GRB10 was over-expressed, and, using enzyme-linked immunosorbent assays for IGF1 and IGF-binding protein-3 (IGFBP3), we found that IGF1 and IGFBP3 were low-expressed in this patient.

Conclusions: We demonstrate that a combination of uncommon, rare and exceptional molecular defects related to the molecular bases of particular birth defects can be analyzed and diagnosed to potentially explain the observed variability in the combination of molecular defects.

No MeSH data available.


Related in: MedlinePlus

Brain MRI images showed a hypoplastic corpus callosum, enlargement of the lateral ventricles and hydrocephalus (a and b)
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Fig3: Brain MRI images showed a hypoplastic corpus callosum, enlargement of the lateral ventricles and hydrocephalus (a and b)

Mentions: A physical examination resulted in the following findings: height, 66 cm (<1 rd percentile); weight, 7.5 kg (<1 rd percentile); head circumference, 52 cm (<3 rd percentile); and BMI, 17.2 kg/m2, indicating a persistent failure to thrive. In addition, the patient had trident hands and fifth finger clinodactyly. An X-ray of the hand showed stubby fingers, metaphyseal enlargement, bilateral slight curvature of the radius and ulna, and delayed bone age. A spine X-ray showed mild scoliosis and kyphosis at the thoracic and lumbar region (Fig. 2), which indicated achondroplasia. A cerebral MRI showed a hypoplastic corpus callosum, enlargement of the lateral ventricles and hydrocephalus (Fig. 3). In addition, he exhibited muscular hypotonia and sleep-related symptoms (e.g., snoring, mouth breathing, observed apneas, and excessive sweating). An ophthalmological examination and neurometabolic investigation were normal. Based on the above clinical phenotype, a diagnosis of SRS-like symptoms and achondroplasia was suspected.Fig. 2


FGFR3 gene mutation plus GRB10 gene duplication in a patient with achondroplasia plus growth delay with prenatal onset.

Yuan H, Huang L, Hu X, Li Q, Sun X, Xie Y, Kong S, Wang X - Orphanet J Rare Dis (2016)

Brain MRI images showed a hypoplastic corpus callosum, enlargement of the lateral ventricles and hydrocephalus (a and b)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4930580&req=5

Fig3: Brain MRI images showed a hypoplastic corpus callosum, enlargement of the lateral ventricles and hydrocephalus (a and b)
Mentions: A physical examination resulted in the following findings: height, 66 cm (<1 rd percentile); weight, 7.5 kg (<1 rd percentile); head circumference, 52 cm (<3 rd percentile); and BMI, 17.2 kg/m2, indicating a persistent failure to thrive. In addition, the patient had trident hands and fifth finger clinodactyly. An X-ray of the hand showed stubby fingers, metaphyseal enlargement, bilateral slight curvature of the radius and ulna, and delayed bone age. A spine X-ray showed mild scoliosis and kyphosis at the thoracic and lumbar region (Fig. 2), which indicated achondroplasia. A cerebral MRI showed a hypoplastic corpus callosum, enlargement of the lateral ventricles and hydrocephalus (Fig. 3). In addition, he exhibited muscular hypotonia and sleep-related symptoms (e.g., snoring, mouth breathing, observed apneas, and excessive sweating). An ophthalmological examination and neurometabolic investigation were normal. Based on the above clinical phenotype, a diagnosis of SRS-like symptoms and achondroplasia was suspected.Fig. 2

Bottom Line: Genotype- and phenotype-level correlations have been found between the clinical symptoms of achondroplasia and achondroplasia-specific FGFR3 mutations.Using quantitative real-time PCR analysis, GRB10 was over-expressed, and, using enzyme-linked immunosorbent assays for IGF1 and IGF-binding protein-3 (IGFBP3), we found that IGF1 and IGFBP3 were low-expressed in this patient.We demonstrate that a combination of uncommon, rare and exceptional molecular defects related to the molecular bases of particular birth defects can be analyzed and diagnosed to potentially explain the observed variability in the combination of molecular defects.

View Article: PubMed Central - PubMed

Affiliation: Guangzhou KingMed Center for Clinical Laboratory Co., Ltd, Guangzhou, 510330, Guangdong, China.

ABSTRACT

Background: Achondroplasia is a well-defined and common bone dysplasia. Genotype- and phenotype-level correlations have been found between the clinical symptoms of achondroplasia and achondroplasia-specific FGFR3 mutations.

Result: A 2-year-old boy with clinical features consistent with achondroplasia and Silver-Russell syndrome-like symptoms was found to carry a mutation in the fibroblast growth factor receptor-3 (FGFR3) gene at c.1138G > A (p.Gly380Arg) and a de novo 574 kb duplication at chromosome 7p12.1 that involved the entire growth-factor receptor bound protein 10 (GRB10) gene. Using quantitative real-time PCR analysis, GRB10 was over-expressed, and, using enzyme-linked immunosorbent assays for IGF1 and IGF-binding protein-3 (IGFBP3), we found that IGF1 and IGFBP3 were low-expressed in this patient.

Conclusions: We demonstrate that a combination of uncommon, rare and exceptional molecular defects related to the molecular bases of particular birth defects can be analyzed and diagnosed to potentially explain the observed variability in the combination of molecular defects.

No MeSH data available.


Related in: MedlinePlus