Identification of novel pathogenic variants in the GNAS gene in children with morbid obesity and pseudohypoparathyroidism
D. A. Kopytina,
O. V. Vasyukova,
R. R. Salakhov,
P. L. Okorokov,
E. V. Kopytina,
E. V. Nagaeva,
R. I. Khusainova,
I. R. Minniakhmetov,
S. V. Popov,
O. B. Bezlepkina,
N. G. Mokrysheva https://doi.org/10.14341/omet13169
Abstract
Pseudohypoparathyroidism (PHP) is a clinically heterogeneous group of rare inherited bone diseases characterized by resistance of target organs to the action of parathormone (PTH) as result of an epi/genetic disorder.
This article describes patients with the phenotype of pseudohypoparathyroidism type 1a in whom two previously undescribed variants in the GNAS gene were identified: NM_000516.7(GNAS):c.586-18_591del, which captures intron 7, exon 8 acceptor splice site and exon 8 splice site resulting in a 24 nucleotide deletion, and NM_000516.7(GNAS):c.201del p.Phe68LeufsTer32 resulting in a reading frame shift and a premature termination codon in two unrelated children with progressive weight gain from birth. According to the pathogenicity evaluation criteria, both variants are categorized as likely pathogenic variants
About the Authors
D. A. Kopytina
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Daria A. Kopytina, MD
11 Dm. Ulyanova street, 117036 Moscow
Competing Interests:
None
O. V. Vasyukova
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Olga V. Vasyukova, MD
11 Dm. Ulyanova street, 117036 Moscow
Competing Interests:
None
R. R. Salakhov
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Ramil R. Salakhov, MD
11 Dm. Ulyanova street, 117036 Moscow
Competing Interests:
None
P. L. Okorokov
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Pavel L. Okorokov, MD
11 Dm. Ulyanova street, 117036 Moscow
Competing Interests:
None
E. V. Kopytina
2Lipetsk City Children’s Hospital
Russian Federation
Competing Interests:
Russian Federation
Elena V. Kopytina, MD
Competing Interests:
None
E. V. Nagaeva
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Elena V. Nagaeva, MD, PhD
11 Dm. Ulyanova street, 117036 Moscow
Competing Interests:
None
R. I. Khusainova
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Rita I. Khusainova, PhD in biology
11 Dm. Ulyanova street, 117036 Moscow
Competing Interests:
None
I. R. Minniakhmetov
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Ildar R. Minniakhmetov, PhD in biology
11 Dm. Ulyanova street, 117036 Moscow
Competing Interests:
None
S. V. Popov
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Sergey V. Popov
11 Dm. Ulyanova street, 117036 Moscow
Competing Interests:
None
O. B. Bezlepkina
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Olga B. Bezlepkina, MD, PhD, Professor
11 Dm. Ulyanova street, 117036 Moscow
Competing Interests:
None
N. G. Mokrysheva
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Natalia G. Mokrysheva, MD, PhD, Professor
11 Dm. Ulyanova street, 117036 Moscow
ResearcherID: AAY-3761-2020
Scopus Author ID: 35269746000
Competing Interests:
None
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1. Figure 1: Phenotypic features in a boy with PHP 1a: A — Brachydactyly and subcutaneous calcinates (radiograph of hand and wrist); B — Moon shaped face, morbid obesity. | |
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2. Figure 2. Variant NM_000516.7(GNAS):c.586-18_591del A. Electrophoregrams of the proband and his parents. B. IGV (graphical browser) plot of the deletion [28]. | |
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3. Figure 3: Phenotypic features in a girl with PHP Ia: A. Brachydactyly (wrist hand radiograph). B. Subcutaneous calcinates. C. Moon-shaped face, morbid obesity. | |
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4. Figure 4: Variant NM_000516.7(GNAS):c.201del, (p.Phe68LeufsTer32) identified in the proband and her mother. | |
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For citations:
Kopytina D.A., Vasyukova O.V., Salakhov R.R., Okorokov P.L., Kopytina E.V., Nagaeva E.V., Khusainova R.I., Minniakhmetov I.R., Popov S.V., Bezlepkina O.B., Mokrysheva N.G. Identification of novel pathogenic variants in the GNAS gene in children with morbid obesity and pseudohypoparathyroidism. Obesity and metabolism. 2024;21(4):412-424. (In Russ.) https://doi.org/10.14341/omet13169
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