Novel Compound Heterozygous Variants in the CDC6 Gene in a Russian Patient with Meier-Gorlin Syndrome

Viktoriia Zabnenkova,1 Olga Shchagina,1 Olga Makienko,2 Galina Matyushchenko,2 Oxana Ryzhkova1 1Molecular Genetics Laboratory № 3 The Shared Resource Centre “Genome”, Federal State Budgetary Scientific Institution Research Centre for Medical Genetics named after Academician N.P. Bochkov,...

Full description

Bibliographic Details
Main Authors: Zabnenkova V, Shchagina O, Makienko O, Matyushchenko G, Ryzhkova O
Format: Article
Language:English
Published: Dove Medical Press 2022-01-01
Series:The Application of Clinical Genetics
Subjects:
Online Access:https://www.dovepress.com/novel-compound-heterozygous-variants-in-the-cdc6-gene-in-a-russian-pat-peer-reviewed-fulltext-article-TACG
_version_ 1818968403286687744
author Zabnenkova V
Shchagina O
Makienko O
Matyushchenko G
Ryzhkova O
author_facet Zabnenkova V
Shchagina O
Makienko O
Matyushchenko G
Ryzhkova O
author_sort Zabnenkova V
collection DOAJ
description Viktoriia Zabnenkova,1 Olga Shchagina,1 Olga Makienko,2 Galina Matyushchenko,2 Oxana Ryzhkova1 1Molecular Genetics Laboratory № 3 The Shared Resource Centre “Genome”, Federal State Budgetary Scientific Institution Research Centre for Medical Genetics named after Academician N.P. Bochkov, Moscow, Russian Federation; 2Counselling Unit, Federal State Budgetary Scientific Institution Research Centre for Medical Genetics named after Academician N.P. Bochkov, Moscow, Russian FederationCorrespondence: Viktoriia ZabnenkovaMolecular Genetics Laboratory № 3 The Shared Resource Centre “Genome”, Federal State Budgetary Scientific Institution Research Centre for Medical Genetics named after Academician N.P. Bochkov, ul. Moskvorechye, 1, Moscow, 115522, Russian FederationTel +7 903 200 92 85Fax +7 499 324 81 10Email V_Zabnenkova@dnalab.ruBackground: Meier-Gorlin syndrome (MGS) is a rare genetic syndrome inherited in an autosomal dominant or autosomal recessive manner. The disorder is characterized by bilateral microtia, absence or hypoplasia of the patella, and an intrauterine growth retardation as well as a number of other characteristic features. The cause of the disease is mutations in genes encoding proteins involved in the regulation of the cell cycle (ORC1, ORC4, ORC6, CDT1, CDC6, GMNN, CDC45L, MCM3, MCM5, MCM7, GINS2, and DONSON). Meier-Gorlin syndrome 5 due to mutations in the CDC6 gene is difficult to diagnose, and few clinical data have been described to date. Only one patient (male) with a missense mutation in a homozygous state has been previously reported. This report describes a new clinical case of Meier-Gorlin syndrome 5. This is also the first report of a Russian patient with Meier-Gorlin syndrome.Case Presentation: The patient, a female, had extremely low physical development, neonatal progeroid appearance, lipodystrophy, thin skin, partial alopecia, cyanosis of the face, triangular face, microgenia, arachnodactyly, delayed bone age, hepatomegaly, hypoplasia of the labia majora, and hypertrophy of the clitoris in addition to known clinical signs. Differential diagnosis was performed with chromosomal abnormalities and Hutchinson-Gilford progeria. According to the results of sequencing of the clinical exome, the patient had two previously undescribed variants in the CDC6 gene, c.230A>G (p.(Lys77Arg)) and c.232C>T (p.(Gln78Ter)), NM_001254.3, in a compound heterozygous state.Conclusion: This case allows us to learn more about the clinical features and nature of MGS 5 and improve the speed of diagnostics and quality of genetic counseling for such families.Keywords: MGS 5, ear-patella-short stature syndrome, CDC6 gene, case report
first_indexed 2024-12-20T14:04:08Z
format Article
id doaj.art-9eff1b0b07604de091644025e9219f3f
institution Directory Open Access Journal
issn 1178-704X
language English
last_indexed 2024-12-20T14:04:08Z
publishDate 2022-01-01
publisher Dove Medical Press
record_format Article
series The Application of Clinical Genetics
spelling doaj.art-9eff1b0b07604de091644025e9219f3f2022-12-21T19:38:18ZengDove Medical PressThe Application of Clinical Genetics1178-704X2022-01-01Volume 1511072061Novel Compound Heterozygous Variants in the CDC6 Gene in a Russian Patient with Meier-Gorlin SyndromeZabnenkova VShchagina OMakienko OMatyushchenko GRyzhkova OViktoriia Zabnenkova,1 Olga Shchagina,1 Olga Makienko,2 Galina Matyushchenko,2 Oxana Ryzhkova1 1Molecular Genetics Laboratory № 3 The Shared Resource Centre “Genome”, Federal State Budgetary Scientific Institution Research Centre for Medical Genetics named after Academician N.P. Bochkov, Moscow, Russian Federation; 2Counselling Unit, Federal State Budgetary Scientific Institution Research Centre for Medical Genetics named after Academician N.P. Bochkov, Moscow, Russian FederationCorrespondence: Viktoriia ZabnenkovaMolecular Genetics Laboratory № 3 The Shared Resource Centre “Genome”, Federal State Budgetary Scientific Institution Research Centre for Medical Genetics named after Academician N.P. Bochkov, ul. Moskvorechye, 1, Moscow, 115522, Russian FederationTel +7 903 200 92 85Fax +7 499 324 81 10Email V_Zabnenkova@dnalab.ruBackground: Meier-Gorlin syndrome (MGS) is a rare genetic syndrome inherited in an autosomal dominant or autosomal recessive manner. The disorder is characterized by bilateral microtia, absence or hypoplasia of the patella, and an intrauterine growth retardation as well as a number of other characteristic features. The cause of the disease is mutations in genes encoding proteins involved in the regulation of the cell cycle (ORC1, ORC4, ORC6, CDT1, CDC6, GMNN, CDC45L, MCM3, MCM5, MCM7, GINS2, and DONSON). Meier-Gorlin syndrome 5 due to mutations in the CDC6 gene is difficult to diagnose, and few clinical data have been described to date. Only one patient (male) with a missense mutation in a homozygous state has been previously reported. This report describes a new clinical case of Meier-Gorlin syndrome 5. This is also the first report of a Russian patient with Meier-Gorlin syndrome.Case Presentation: The patient, a female, had extremely low physical development, neonatal progeroid appearance, lipodystrophy, thin skin, partial alopecia, cyanosis of the face, triangular face, microgenia, arachnodactyly, delayed bone age, hepatomegaly, hypoplasia of the labia majora, and hypertrophy of the clitoris in addition to known clinical signs. Differential diagnosis was performed with chromosomal abnormalities and Hutchinson-Gilford progeria. According to the results of sequencing of the clinical exome, the patient had two previously undescribed variants in the CDC6 gene, c.230A>G (p.(Lys77Arg)) and c.232C>T (p.(Gln78Ter)), NM_001254.3, in a compound heterozygous state.Conclusion: This case allows us to learn more about the clinical features and nature of MGS 5 and improve the speed of diagnostics and quality of genetic counseling for such families.Keywords: MGS 5, ear-patella-short stature syndrome, CDC6 gene, case reporthttps://www.dovepress.com/novel-compound-heterozygous-variants-in-the-cdc6-gene-in-a-russian-pat-peer-reviewed-fulltext-article-TACGmgs 5ear-patella-short stature syndromecdc6 genecase report
spellingShingle Zabnenkova V
Shchagina O
Makienko O
Matyushchenko G
Ryzhkova O
Novel Compound Heterozygous Variants in the CDC6 Gene in a Russian Patient with Meier-Gorlin Syndrome
The Application of Clinical Genetics
mgs 5
ear-patella-short stature syndrome
cdc6 gene
case report
title Novel Compound Heterozygous Variants in the CDC6 Gene in a Russian Patient with Meier-Gorlin Syndrome
title_full Novel Compound Heterozygous Variants in the CDC6 Gene in a Russian Patient with Meier-Gorlin Syndrome
title_fullStr Novel Compound Heterozygous Variants in the CDC6 Gene in a Russian Patient with Meier-Gorlin Syndrome
title_full_unstemmed Novel Compound Heterozygous Variants in the CDC6 Gene in a Russian Patient with Meier-Gorlin Syndrome
title_short Novel Compound Heterozygous Variants in the CDC6 Gene in a Russian Patient with Meier-Gorlin Syndrome
title_sort novel compound heterozygous variants in the cdc6 gene in a russian patient with meier gorlin syndrome
topic mgs 5
ear-patella-short stature syndrome
cdc6 gene
case report
url https://www.dovepress.com/novel-compound-heterozygous-variants-in-the-cdc6-gene-in-a-russian-pat-peer-reviewed-fulltext-article-TACG
work_keys_str_mv AT zabnenkovav novelcompoundheterozygousvariantsinthecdc6geneinarussianpatientwithmeiergorlinsyndrome
AT shchaginao novelcompoundheterozygousvariantsinthecdc6geneinarussianpatientwithmeiergorlinsyndrome
AT makienkoo novelcompoundheterozygousvariantsinthecdc6geneinarussianpatientwithmeiergorlinsyndrome
AT matyushchenkog novelcompoundheterozygousvariantsinthecdc6geneinarussianpatientwithmeiergorlinsyndrome
AT ryzhkovao novelcompoundheterozygousvariantsinthecdc6geneinarussianpatientwithmeiergorlinsyndrome