A case report and literature review of monoallelic mutation of GHR

2019 ◽  
Vol 32 (4) ◽  
pp. 415-419
Author(s):  
Marie Mitani ◽  
Hirohito Shima ◽  
Takeshi Sato ◽  
Tomohiro Inoguchi ◽  
Tsutomu Kamimaki ◽  
...  
Keyword(s):  
Short Stature ◽  
Novel Mutation ◽  
Serum Insulin ◽  
The Novel ◽  
Gh Secretion ◽  
Old Japanese ◽  
Missense Variation ◽  
Normal Stature ◽  
Monoallelic Mutation ◽  
Severe Short Stature

Abstract Background Monoallelic mutations of GHR have been described in idiopathic short stature (ISS), although the significance of these remain unclear. We report a case of ISS with novel monoallelic S219L mutation of GHR and discuss the possible significance of monoallelic GHR mutation in ISS. Case presentation The proband, a 13.9-year-old Japanese boy, had severe short stature (−3.8 standard deviation [SD]). Serum insulin-like growth factor (IGF)-I level and growth hormone (GH) secretion was normal. His parents were nonconsanguineous and had normal stature. Genetic analyses revealed a novel monoallelic missense variation in exon 7 of GHR (S219L). The proband’s mother had the same variation. S219L might be the novel mutation judging from there being no registration of it as a single-nucleotide polymorphism (SNP) in any database, evolutional conservation of Ser219, in silico analyses, and computational molecular visualization analysis. Furthermore, a review of the literature showed that the median height of missense mutation carriers of GHR was relatively low. Conclusions We propose the possibility that monoallelic mutation of GHR increases the susceptibility to short stature.

scholarly journals Urinary Growth Hormone Excretion as Measured by a Sensitive Immunochemiluminometric Assay

1993 ◽  
Vol 30 (2) ◽  
pp. 180-185 ◽  
Author(s):  
G Turner ◽  
R C Brown ◽  
I Weeks ◽  
G E Butler ◽  
F N Creagh ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Individual Variability ◽  
Height Velocity ◽  
Growth Disorders ◽  
Serum Growth Hormone ◽  
Renal Handling ◽  
Gh Secretion ◽  
Normal Stature ◽  
Optimum Sampling

A sensitive immunochemiluminometric assay with a detection limit of 1 · 1μU/L was developed for the measurement of urinary growth hormone (UGH). The assay was shown to be specific and precise. There was a good correlation between serum growth hormone (GH) and UGH concentrations in 20 patients with acromegaly and six volunteers following an intravenous injection of recombinant GH. We concluded therefore that UGH measurements appear to provide a satisfactory index of GH secretion. The use of the assay in the investigation of growth disorders was assessed. We studied 11 pre-pubertal children, six of normal stature, and five of short stature, over a 6-month period. Sequential fortnightly measurements of UGH were carried out and height velocity was determined. The children of short stature grew at a slower rate and excreted less GH than the children of normal stature. However, we observed considerable within-individual variability in GH excretion in both groups (CV 22–98%). We therefore recommend that sequential UGH analyses should be carried out and the results interpreted in conjunction with growth measurements. However, further investigations into the renal handling of GH are needed to establish optimum sampling regimes.

scholarly journals X-linked mental retardation and severe short stature with a novel mutation of the KDM5C gene

2021 ◽  
Vol 30 (1) ◽  
pp. 61-64
Author(s):  
Fumika Kawano-Matsuda ◽  
Tomoki Maeda ◽  
Tadashi Kaname ◽  
Kumiko Yanagi ◽  
Kenji Ihara
Keyword(s):  
Mental Retardation ◽  
Short Stature ◽  
Novel Mutation ◽  
Severe Short Stature ◽  
I Gene

Growth Hormone Insensitivity and Severe Short Stature in Siblings: A Novel Mutation at the Exon 13-Intron 13 Junction of the STAT5b Gene

2007 ◽  
Vol 68 (5) ◽  
pp. 218-224 ◽  
Author(s):  
Vivian Hwa ◽  
Cecilia Camacho-Hübner ◽  
Brian M. Little ◽  
Alessia David ◽  
Lou A. Metherell ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Novel Mutation ◽  
Growth Hormone Insensitivity ◽  
Severe Short Stature ◽  
I Gene

scholarly journals A novel mutation in the ACAN gene in a family with autosomal dominant short stature and intervertebral disc disease

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Noboru Uchida ◽  
Hironori Shibata ◽  
Gen Nishimura ◽  
Tomonobu Hasegawa
Keyword(s):  
Intervertebral Disc ◽  
Short Stature ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Bone Age ◽  
Heterozygous Mutation ◽  
Intervertebral Disc Disease ◽  
Disc Disease ◽  
The Family ◽  
Old Japanese

AbstractHeterozygous mutations in the ACAN gene have been reported in individuals with short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans. We report a family with a phenotypic constellation carrying a novel mutation in the ACAN gene. The proband was a 7-year-old Japanese girl with short stature. Her mother and maternal grandmother also had short stature and intervertebral disc disease. We analyzed the ACAN gene in the family and identified a novel heterozygous mutation: c.4634delT, Leu1545Profs*11.

Growth hormone therapy in a child with severe short stature due to Miller-McKusick-Malvaux (3M) syndrome-2

2019 ◽  
Author(s):  
Sumudu Seneviratne ◽  
Deepthi de Silva ◽  
Emily Cottrell ◽  
Piumi Kuruppu ◽  
KSH de Silva ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Therapy ◽  
Short Stature ◽  
Growth Hormone Therapy ◽  
Severe Short Stature

scholarly journals Delayed diagnosis of Peutz–Jeghers syndrome due to pathological information loss or mistake in family/personal history

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yu-Liang Jiang ◽  
Xiao-Dong Xu ◽  
Bai-Rong Li ◽  
En-Da Yu ◽  
Zi-Ye Zhao ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Novel Mutation ◽  
Delayed Diagnosis ◽  
Personal History ◽  
Pathological Examination ◽  
The Novel ◽  
Novel Mutations ◽  
The Family ◽  
Genetic Level ◽  
Peutz Jeghers Syndrome

Abstract Objective To report Peutz–Jeghers syndrome (PJS) cases with non-definitive clues in the family or personal history and finally diagnosed through pathological examination and STK11 gene mutation test. Clinical presentation and intervention PJS was suspected in 3 families with tortuous medical courses. Two of them had relatives departed due to polyposis or colon cancer without pathological results, and the other one had been diagnosed as hyperplastic polyposis before. Diagnosis of PJS was confirmed by endoscopy and repeated pathological examinations, and the STK11 mutation test finally confirmed the diagnosis at genetic level, during which 3 novel mutation were detected (536C > A, 373_374insA, 454_455insGGAGAAGCGTTTCCCAGTGTGCC). Conclusion Early diagnosis of PJS is important and may be based on a family history with selective features among family members, and the pathological information is the key. The novel mutations also expand the STK11 variant spectrum.

scholarly journals Mutations of uncertain significance in heterozygous variants as a possible cause of severe short stature: a case report

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Nami Mohammadian Khonsari ◽  
Sahar Mohammad Poor Nami ◽  
Benyamin Hakak-Zargar ◽  
Tessa Voth
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Hormone Receptors ◽  
Bone Growth ◽  
Synergistic Effects ◽  
Signs And Symptoms ◽  
Bone Age ◽  
Pathogenic Mutation ◽  
Paracrine Factors ◽  
Severe Short Stature

Abstract Background Linear bone growth is achieved by the division of chondrocytes at the growth plate and is regulated by endocrine and paracrine factors such as growth hormone. Mutations that negatively affect chondrogenesis can be a contributor to short stature. One such mutation can occur in the ACAN gene, causing short stature and advanced bone age. Similarly, mutations in growth hormone receptors (GHR) can lead to Laron syndrome (LS), one of the several disorders that are collectively called growth hormone insensitivity syndrome (GHI). Another example is Floating-Harbor syndrome (FHS), a rare autosomal dominant due to mutations in the SRCAP gene that can also result in short stature. Case presentation We report the case of a 6-year-old female with concomitant mutations in the three genes mentioned above. The mutations reported here were found on genetic studies and are usually benign, causing a variant of undetermined significance. However, our patient’s phenotype could only be explained by the compounded effects of pathogenic mutations of these genes. Some of the same mutations were also found in the patient’s father and her paternal grandfather. Both also presented with short stature, though not to the same degree as our patient. While these mutations are often reported to be insignificant, they gave rise to severe short stature and a specific phenotype in the patient when presented together. We think that even though the GHI spectrum is inherited through an autosomal recessive pattern, the sum of these heterozygous mutations resulted in severe short stature despite the limited GHI seen in our patient, the father, and the grandfather, through a rare ACAN and SRCAP mutation that, to our knowledge, has not been previously reported as a pathogenic mutation in the literature. Conclusion We investigated the possible synergistic effects of these variations on exacerbation or masking of the signs and symptoms of GHI with the hope of providing a better understanding of these genes and their function through our rare case.

scholarly journals Autosomal recessive chondrodysplasia with severe short stature caused by a biallelic COL10A1 variant

2017 ◽  
Vol 55 (6) ◽  
pp. 403-407 ◽  
Author(s):  
Noor ul Ain ◽  
Outi Makitie ◽  
Sadaf Naz
Keyword(s):  
Short Stature ◽  
Skeletal Dysplasia ◽  
In Silico ◽  
Autosomal Recessive ◽  
Limb Deformity ◽  
Mild Phenotype ◽  
Whole Exome ◽  
New Type ◽  
Severe Short Stature ◽  
Amino Acid Conservation

BackgroundHeterozygous mutations in COL10A1 underlie metaphyseal chondrodysplasia, Schmid type (MCDS), an autosomal dominant skeletal dysplasia.ObjectiveTo identify the causative variant in a large consanguineous Pakistani family with severe skeletal dysplasia and marked lower limb deformity.MethodsWhole exome sequencing was completed followed by Sanger sequencing to verify segregation of the identified variants. In silico variant pathogenicity predictions and amino acid conservation analyses were performed.ResultsA homozygous c.133 C>T (p.Pro45Ser) variant was identified in COL10A1 in all six severely affected individuals (adult heights 119–130 cm, mean ~−6.33 SD). The individuals heterozygous for the variant had mild phenotype of short stature (adult heights 140–162 cm, mean ~−2.15 SD) but no apparent skeletal deformities. The variant was predicted to be pathogenic by in silico prediction tools and was absent from public databases and hundred control chromosomes. Pro45 is conserved in orthologues and is located in the non-collagenous 2 domain of COL10A1, variants of which have never been associated with skeletal dysplasia.ConclusionsThis first report of individuals with a homozygous variant in COL10A1 defines a new type of autosomal recessive skeletal dysplasia. The observations in COL10A1 variant carriers suggest a phenotypic overlap between the mildest forms of MCDS and idiopathic short stature.

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