scholarly journals The role of molecular genetic methods in the diagnosis of McCune—Albright syndrome

2018 ◽  
Vol 63 (6) ◽  
pp. 360-368
Author(s):  
Nadezhda V. Makazan ◽  
Elizaveta M. Orlova ◽  
Anna A. Kolodkina ◽  
Maria A. Kareva ◽  
Natalia Yu. Kalinchenko ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Somatic Mutations ◽  
Molecular Genetic ◽  
Mccune Albright Syndrome ◽  
Gnas Gene ◽  
Allele Specific ◽  
Taqman Pcr ◽  
Polymerase Chain ◽  
Albright Syndrome ◽  
Next Generation Sequencing Ngs

McCune-Albright syndrome (MAS) is a rare genetic disorder which is caused by somatic mutations in the GNAS gene. Clinical symptoms of MAS include café-au-lait skin pigmentation, fibrous dysplasia, and autonomous endocrine hyperfunction. Somatic character of the gene defects determines wide variety of syndrome manifestations, from mild forms with minimum presentation to severe conditions with aggressive course. Potential multicomponent form of the MAS syndrome necessitates the dynamic monitoring, including regular screening for possible components of the disease. Therefore, additional methods specifying the diagnosis of MAS syndrome, especially of its suppressed forms, should facilitate selection of patient management strategy and monitoring rate and/or complete exclusion of the diagnosis. Molecular genetic verification of the diagnosis may be one of these methods. Objective — the study was aimed at evaluating massive parallel sequencing (next generation sequencing, NGS) and real-time polymerase chain reaction using the TaqMan technique for detection of somatic mutations (competitive allele-specific TaqMan PCR, CAST-PCR) in the diagnosis of somatic mutations R201C and R201H in the GNAS gene based on DNA obtained from the peripheral blood. Material and methods. The study included patients diagnosed with and suspected for MAS syndrome. Molecular genetic testing of R201C and R201H mutations in the GNAS gene based on DNA extracted from peripheral blood leukocytes was carried out by Next generation sequencing (NGS) and real-time polymerase chain reaction methods using the TaqMan technique for detection of somatic mutations (competitive allele-specific TaqMan PCR, CAST-PCR). Based on clinical data, patients were divided into groups depending on the severity of the disease and the number of MAS manifestations. The results were evaluated by comparing the rate of detected molecular genetic defects in the formed groups of patients. Results. Molecular genetic study included 39 children with MAS syndrome and 6 children with suspected MAS. R201C and R201H mutations in GNAS gene were detected in 16 patients with severe to moderate MAS 16 (41%) 39. No mutations were detected in other MAS patients and patients with suspected MAS. Conclusion. NGS and CAST-PCR methods can detect the presence of mutant alleles R201C and R201H of GNAS gene in DNA samples obtained from the blood in the case of severe to moderate MAS syndrome, but they cannot be recommended for MAS diagnosis based on the peripheral blood samples in children with mild signs of the syndrome or suspected diagnosis.

scholarly journals McCune-Albright Syndrome with Acromegaly and Fibrous Dysplasia Associated with the GNAS Gene Mutation Identified by Sensitive PNA-clamping Method

2007 ◽  
Vol 46 (18) ◽  
pp. 1577-1583 ◽  
Author(s):  
Mari Imanaka ◽  
Keiji Iida ◽  
Hitoshi Nishizawa ◽  
Hidenori Fukuoka ◽  
Ryoko Takeno ◽  
...  
Keyword(s):  
Fibrous Dysplasia ◽  
Gene Mutation ◽  
Mccune Albright Syndrome ◽  
Gnas Gene ◽  
Albright Syndrome ◽  
Gnas Gene Mutation ◽  
Mccune Albright

scholarly journals Detection of Gene Mutation for Patients with McCune- Albright Syndrome and Diagnosis Experience: A Report of Two Cases and Literature Review

2021 ◽  
Vol 8 (7) ◽  
Author(s):  
Sun L ◽  
◽  
Yan S ◽  
Gao H ◽  
Yuan C ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Peripheral Blood ◽  
Clinical Symptoms ◽  
Ovarian Tissue ◽  
Cystic Mass ◽  
Mccune Albright Syndrome ◽  
Detection Techniques ◽  
Albright Syndrome ◽  
The Right ◽  
Mccune Albright

Background: McCune-Albright Syndrome (MAS) is a rare disease characterized by a broad spectrum of syndromes, including hyperfunctioning endocrinopathies, café-au-lait leisions, and multiple bone fibrous dysplasias. The diagnosis of MAS is usually based on clinical symptoms. However, most of MAS patients may not display typical symptoms, which make the early diagnosis and treatment of MAS difficult. Cases: Patient 1, a 7-year and 4-month-old girl, developed vaginal bleeding with no apparent cause. A Café-au-lait macule patch could be seen on the right trunk. E2 was 914pmol/L. FSH <0.1IU/L, Luteinizing Hormone (LH) <0.1IU/L. Performing ultrasound, there was a cystic mass in the left accessory area with ovarian echo. There were bone abnormalities in the long bones of the extremities. Patient 2, a girl aged 4 years and 9 months, has abnormal enlarged breasts with no obvious cause. There was a cystic mass in the left accessory area with ovarian echo No apparent Café-au-lait macule hyperpigmented skin macule was seen. E2 is 800pg/ml, FSH <0.1IU/L, LH is 0.2IU/L. GNAS mutation were both positive in the cyst tissue but was negative in the peripheral blood. Conclusion: Gene sequencing is the confirmable proof in diagnosis of MAS. Negative GNAS gene mutation results in the peripheral blood and skin cannot completely rule out the possibility of MAS. Biopsy of the lesion tissues, such as ovarian tissue, may present more efficient results. New detection techniques have higher sensitivity and make molecular diagnosis more accurate.

scholarly journals Molecular selection of Beta vulgaris L. breeding materials with genes of resistance to abiotic stresses

2019 ◽  
Vol 1 (1) ◽  
pp. 16-20
Author(s):  
A. A. Nalbandyan ◽  
T. P. Fedulova ◽  
A. S. Hussein
Keyword(s):  
Sugar Beet ◽  
Molecular Genetic ◽  
Polymerase Chain Reaction Method ◽  
Root Knot Nematode ◽  
Chain Reaction ◽  
Specific Primers ◽  
Allele Specific ◽  
Molecular Selection ◽  
Polymerase Chain ◽  
Selection Of

In the work, the results of sugar beet breeding materials' molecular-genetic studying for presence of genes of resistance to root-knot nematode, rhizomania and powdery mildew are presented. Testing of plants was conducted using polymerase chain reaction method. The genes R6m-1, Rz1 and Rz2, Pm were identified with the help of 5 one-chain RAPD and 4 allele-specific primers. Aim of the studies is to screen sugar beet varieties for presence of the abovementioned genes of resistance. Domestic and foreign sugar beet hybrids were an object of the studies.

scholarly journals The “Phantom of the Opera” sign of craniofacial fibrous dysplasia with unilateral polyostotic involvement in McCune-Albright syndrome

2017 ◽  
Vol 4 (2) ◽  
pp. 43
Author(s):  
W. Phillip Law ◽  
Peter Jackson
Keyword(s):  
Fibrous Dysplasia ◽  
Genetic Disorder ◽  
Polyostotic Fibrous Dysplasia ◽  
Skeletal Scintigraphy ◽  
Facial Bones ◽  
Mccune Albright Syndrome ◽  
Café Au Lait Spots ◽  
Gnas Gene ◽  
Albright Syndrome ◽  
Mccune Albright

McCune-Albright syndrome is a very rare genetic disorder resulting from a sporadically occurring somatic \textit{GNAS} gene mutation. It is characterised by the association of: endocrinopathy (most commonly precocious puberty), polyostotic fibrous dysplasia, and cutaneous pigmentation with café-au-lait spots with edges resembling the coast of Maine. We present a case of McCune-Albright syndrome with unilateral polyostotic fibrous dysplasia including involvement of the skull and facial bones on one side resulting in an appearance on skeletal scintigraphy resembling the characteristic mask of the “Phantom of the Opera”.

scholarly journals Genetics of Acromegaly and Gigantism

2021 ◽  
Vol 10 (7) ◽  
pp. 1377
Author(s):  
Anna Bogusławska ◽  
Márta Korbonits
Keyword(s):  
Pituitary Adenoma ◽  
Somatic Mutations ◽  
Final Height ◽  
Pituitary Tumour ◽  
Carney Complex ◽  
Mccune Albright Syndrome ◽  
Albright Syndrome ◽  
Gene Panels ◽  
Genetically Determined

Growth hormone (GH)-secreting pituitary tumours represent the most genetically determined pituitary tumour type. This is true both for germline and somatic mutations. Germline mutations occur in several known genes (AIP, PRKAR1A, GPR101, GNAS, MEN1, CDKN1B, SDHx, MAX) as well as familial cases with currently unknown genes, while somatic mutations in GNAS are present in up to 40% of tumours. If the disease starts before the fusion of the epiphysis, then accelerated growth and increased final height, or gigantism, can develop, where a genetic background can be identified in half of the cases. Hereditary GH-secreting pituitary adenoma (PA) can manifest as isolated tumours, familial isolated pituitary adenoma (FIPA) including cases with AIP mutations or GPR101 duplications (X-linked acrogigantism, XLAG) or can be a part of systemic diseases like multiple endocrine neoplasia type 1 or type 4, McCune–Albright syndrome, Carney complex or phaeochromocytoma/paraganglioma-pituitary adenoma association. Family history and a search for associated syndromic manifestations can help to draw attention to genetic causes; many of these are now tested as part of gene panels. Identifying genetic mutations allows appropriate screening of associated comorbidities as well as finding affected family members before the clinical manifestation of the disease. This review focuses on germline and somatic mutations predisposing to acromegaly and gigantism.

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