scholarly journals Chitayat-Hall and Schaaf-Yang syndromes:a common aetiology: expanding the phenotype of MAGEL2-related disorders

2018 ◽  
Vol 55 (5) ◽  
pp. 316-321 ◽  
Author(s):  
Rebekah Jobling ◽  
Dimitri James Stavropoulos ◽  
Christian R Marshall ◽  
Cheryl Cytrynbaum ◽  
Michelle M Axford ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Clinical Manifestations ◽  
Rare Condition ◽  
Hormone Deficiency ◽  
Truncated Protein ◽  
Dysmorphic Features ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
And Inversion

BackgroundChitayat-Hall syndrome, initially described in 1990, is a rare condition characterised by distal arthrogryposis, intellectual disability, dysmorphic features and hypopituitarism, in particular growth hormone deficiency. The genetic aetiology has not been identified.Methods and resultsWe identified three unrelated families with a total of six affected patients with the clinical manifestations of Chitayat-Hall syndrome. Through whole exome or whole genome sequencing, pathogenic variants in the MAGEL2 gene were identified in all affected patients. All disease-causing sequence variants detected are predicted to result in a truncated protein, including one complex variant that comprised a deletion and inversion.ConclusionsChitayat-Hall syndrome is caused by pathogenic variants in MAGEL2 and shares a common aetiology with the recently described Schaaf-Yang syndrome. The phenotype of MAGEL2-related disorders is expanded to include growth hormone deficiency as an important and treatable complication.

scholarly journals MOLECULAR GENETIC CHARACTERISTICS CHILDREN WITH GROWTHHORMONE DEFICIENCY

2017 ◽  
Vol 9 (4) ◽  
pp. 12-16
Author(s):  
O S Berseneva ◽  
A S Glotov ◽  
O S Glotov ◽  
E A Serebryakova ◽  
T E Ivashenko ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Genetic Studies ◽  
Genetic Characteristics ◽  
Therapeutic Algorithms ◽  
Congenital Hypopituitarism

Clinical manifestations of heterogeneity of growth hormone deficiency when definitive results of hormonal stimulus test determines the need to search for molecular genetic markers of the disease to form personalized therapeutic algorithms. Molecular genetic analysis in patients with congenital hypopituitarism was carried out by new-generation sequencing (NGS) with "Amplisek" technology. All patients with congenital hypopituitarism, who are in a special registry of Saint Petersburg, were included in this study. differences in the frequency of detection of mutations in patients with multiple anterior pituitary hormone deficiency and in patients with isolated growth hormone deficiency were found. The mutation frequency of diagnosis in genes responsible for congenital hypopituitarism in patients of St. Petersburg were studied.Mutations in genes associated with congenital hypopituitarism were identified in 16.3% of patients with pituitary dwarfism (16 of 98). The most commonly diagnosed mutations are changes in gene PROP1. In carrying out the molecular genetic studies of patients with congenital hypopituitarism is necessary to consider the likelihood of the presence of these rare pathologies such as loss of genes GHSR, ARNT2, BTK. Currently conducting molecular genetic studies in patients with congenital hypopituitarism further predicts development of the disease and, if necessary, adjust the ongoing replacement therapy.

scholarly journals Whole Exome Sequencing Uncovered the Genetic Architecture of Growth Hormone Deficiency Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Chenxi Yu ◽  
Bobo Xie ◽  
Zhengye Zhao ◽  
Sen Zhao ◽  
Lian Liu ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Molecular Diagnosis ◽  
Hormone Deficiency ◽  
Clinical Criteria ◽  
Mutational Burden ◽  
Group I ◽  
Whole Exome

PurposeCongenital growth hormone deficiency (GHD) is a rare and etiologically heterogeneous disease. We aim to screen disease-causing mutations of GHD in a relatively sizable cohort and discover underlying mechanisms via a candidate gene-based mutational burden analysis.MethodsWe retrospectively analyzed 109 short stature patients associated with hormone deficiency. All patients were classified into two groups: Group I (n=45) with definitive GHD and Group II (n=64) with possible GHD. We analyzed correlation consistency between clinical criteria and molecular findings by whole exome sequencing (WES) in two groups. The patients without a molecular diagnosis (n=90) were compared with 942 in-house controls for the mutational burden of rare mutations in 259 genes biologically related with the GH axis.ResultsIn 19 patients with molecular diagnosis, we found 5 possible GHD patients received known molecular diagnosis associated with GHD (NF1 [c.2329T>A, c.7131C>G], GHRHR [c.731G>A], STAT5B [c.1102delC], HRAS [c.187_207dup]). By mutational burden analysis of predicted deleterious variants in 90 patients without molecular diagnosis, we found that POLR3A (p = 0.005), SUFU (p = 0.006), LHX3 (p = 0.021) and CREB3L4 (p = 0.040) represented top genes enriched in GHD patients.ConclusionOur study revealed the discrepancies between the laboratory testing and molecular diagnosis of GHD. These differences should be considered when for an accurate diagnosis of GHD. We also identified four candidate genes that might be associated with GHD.

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