Hypochondroplasia in a Child With 1620c&gt;G (Asn540lys) Mutation in FGFR3

Korkmaz, Hüseyin Anıl; Hazan, Fılız; Dizdarer, Ceyhun; Tükün, Ajlan

doi:10.4274/jcrpe.787

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…[21] Some studies showed that individuals with the FGFR3 N540K mutation may have an increased incidence of mild to moderate intellectual disability or learning disabilities. [42] However, Song et al (1999) suggested that the clinical findings were similar in 2 groups of HCH with or without FGFR3 mutations, only the radiological findings of mesomelia of upper and lower limbs and, L1/L4 ratio in anterior–posterior and lateral view were more typical in HCH with FGFR3 mutations than in HCH without FGFR3 mutations. [8] De Rosa et al described a 16-month-old male with N540K homozygous mutation in the FGFR3 gene who showed a more severe phenotype than the usual heterozygous HCH, which was even shorter than the heterozygous ACH.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel mutation of FGFR3 gene in a large Chinese pedigree with hypochondroplasia by next-generation sequencing

Yao

Wang

et al. 2019

Medicine

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Rationale:Hypochondroplasia (HCH) is the mildest form of chondrodysplasia characterized by disproportionate short stature, short extremities, and variable lumbar lordosis. It is caused by mutations in fibroblast growth factor receptor 3 (FGFR3) gene. Up to date, at least thirty mutations of FGFR3 gene have been found to be related to HCH. However, mutational screening of the FGFR3 gene is still far from completeness. Identification of more mutations is particularly important in diagnosis of HCH and will gain more insights into the molecular basis for the pathogenesis of HCH.Patient concerns:A large Chinese family consisting of 53 affected individuals with HCH phenotypes was examined.Diagnoses:A novel missense mutation, c.1052C>T, in FGFR3 gene was identified in a large Chinese family with HCH. On the basis of this finding and clinical manifestations, the final diagnosis of HCH was made.Interventions:Next-generation sequencing (NGS) of DNA samples was performed to detect the mutation in the chondrodysplasia-related genes on the proband and her parents, which was confirmed by Sanger sequencing in the proband and most of other living affected family members.Outcomes:A novel missense mutation, c.1052C>T, in the extracellular, ligand-binding domain of FGFR3 was identified in a large Chinese family with HCH. This heterozygous mutation results in substitution of serine for phenylalanine at amino acid 351 (p.S351F) and co-segregates with the phenotype in this family. Molecular docking analysis reveals that this unique FGFR3 mutation results in an enhancement of ligand-binding affinity between FGFR3 and its main ligand, fibroblast growth factor 9.Lessons:This novel mutation is the first mutation displaying an increase in ligand-binding affinity, therefore it may serve as a model to investigate ligand-dependent activity of FGF-FGFR complex. Our data also expanded the mutation spectrum of FGFR3 gene and facilitated clinic diagnosis and genetic counseling for this family with HCH.

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Section: Discussionmentioning

confidence: 99%

Identification of a novel mutation of FGFR3 gene in a large Chinese pedigree with hypochondroplasia by next-generation sequencing

Yao

Wang

et al. 2019

Medicine

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“…Arm span is an important measure in the assessment of short-limbed short stature (or long-limbed high height) resulting from growth hormone deficiency, chromosomal disorders (Turner syndrome, Marfan syndrome, etc.) and skeletal dysplasia (achondroplasia, hypochondroplasia, rickets and so on) in children [ 1 – 4 ]. In an epidemiological survey, with a large number of subjects’ indicators, it is especially valuable to establish methods which can measure both quickly and accurately.…”

Section: Introductionmentioning

confidence: 99%

Comparative study on three different methods for arm-span measurement: the Japan environment and Children’s study pilot

Tsuji

Ayabe

Tanaka

et al. 2017

Environ Health Prev Med

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BackgroundArm span is an important measure for the assessment of growth and hormone deficiency diseases. In an epidemiological survey, with a large number of subjects’ indicators, it is especially valuable to establish methods which can measure both quickly and accurately. However, there are various methods, and the length of arm span may vary according to the medical institution.MethodsThe arm span of nine 6-year old subjects was measured using two institutional standard methods, A and B, and a third method C which is an improved method and has been used for the first time in this study. A, No-Wall, with heels together the child stretches the arms out to the sides. B, Wall & No-Line, the child stands against the wall with heels together and spreads the arms against the wall. C, Wall & Line, the method is the same as B except a paper with horizontal lines is placed on the wall. We measured twice by each method.ResultsThe difference between the 1st and 2nd measurements was marginally significantly smaller by using method of C.ConclusionThe method C, which we improved, is the best way to measure arm span.

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