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Maternal Uniparental Disomy of Chromosome 20 (UPD(20)mat) as Differential Diagnosis of Silver Russell Syndrome: Identification of Three New Cases
Silver Russell Syndrome (SRS, MIM #180860) is a rare growth retardation disorder in which clinical diagnosis is based on six features: pre- and postnatal growth failure, relative macrocephaly, prominent forehead, body asymmetry, and feeding difficulties (Netchine–Harbison clinical scoring system (NH...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073552/ https://www.ncbi.nlm.nih.gov/pubmed/33920573 http://dx.doi.org/10.3390/genes12040588 |
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author | Tannorella, Pierpaola Minervino, Daniele Guzzetti, Sara Vimercati, Alessandro Calzari, Luciano Patti, Giuseppa Maghnie, Mohamad Allegri, Anna Elsa Maria Milani, Donatella Scuvera, Giulietta Mariani, Milena Modena, Piergiorgio Selicorni, Angelo Larizza, Lidia Russo, Silvia |
author_facet | Tannorella, Pierpaola Minervino, Daniele Guzzetti, Sara Vimercati, Alessandro Calzari, Luciano Patti, Giuseppa Maghnie, Mohamad Allegri, Anna Elsa Maria Milani, Donatella Scuvera, Giulietta Mariani, Milena Modena, Piergiorgio Selicorni, Angelo Larizza, Lidia Russo, Silvia |
author_sort | Tannorella, Pierpaola |
collection | PubMed |
description | Silver Russell Syndrome (SRS, MIM #180860) is a rare growth retardation disorder in which clinical diagnosis is based on six features: pre- and postnatal growth failure, relative macrocephaly, prominent forehead, body asymmetry, and feeding difficulties (Netchine–Harbison clinical scoring system (NH-CSS)). The molecular mechanisms consist in (epi)genetic deregulations at multiple loci: the loss of methylation (LOM) at the paternal H19/IGF2:IG-DMR (chr11p15.5) (50%) and the maternal uniparental disomy of chromosome 7 (UPD(7)mat) (10%) are the most frequent causes. Thus far, about 40% of SRS remains undiagnosed, pointing to the need to define the rare mechanisms in such a consistent fraction of unsolved patients. Within a cohort of 176 SRS with an NH-CSS ≥ 3, a molecular diagnosis was disclosed in about 45%. Among the remaining patients, we identified in 3 probands (1.7%) with UPD(20)mat (Mulchandani–Bhoj–Conlin syndrome, OMIM #617352), a molecular mechanism deregulating the GNAS locus and described in 21 cases, characterized by severe feeding difficulties associated with failure to thrive, preterm birth, and intrauterine/postnatal growth retardation. Our patients share prominent forehead, feeding difficulties, postnatal growth delay, and advanced maternal age. Their clinical assessment and molecular diagnostic flowchart contribute to better define the characteristics of this rare imprinting disorder and to rank UPD(20)mat as the fourth most common pathogenic molecular defect causative of SRS. |
format | Online Article Text |
id | pubmed-8073552 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80735522021-04-27 Maternal Uniparental Disomy of Chromosome 20 (UPD(20)mat) as Differential Diagnosis of Silver Russell Syndrome: Identification of Three New Cases Tannorella, Pierpaola Minervino, Daniele Guzzetti, Sara Vimercati, Alessandro Calzari, Luciano Patti, Giuseppa Maghnie, Mohamad Allegri, Anna Elsa Maria Milani, Donatella Scuvera, Giulietta Mariani, Milena Modena, Piergiorgio Selicorni, Angelo Larizza, Lidia Russo, Silvia Genes (Basel) Article Silver Russell Syndrome (SRS, MIM #180860) is a rare growth retardation disorder in which clinical diagnosis is based on six features: pre- and postnatal growth failure, relative macrocephaly, prominent forehead, body asymmetry, and feeding difficulties (Netchine–Harbison clinical scoring system (NH-CSS)). The molecular mechanisms consist in (epi)genetic deregulations at multiple loci: the loss of methylation (LOM) at the paternal H19/IGF2:IG-DMR (chr11p15.5) (50%) and the maternal uniparental disomy of chromosome 7 (UPD(7)mat) (10%) are the most frequent causes. Thus far, about 40% of SRS remains undiagnosed, pointing to the need to define the rare mechanisms in such a consistent fraction of unsolved patients. Within a cohort of 176 SRS with an NH-CSS ≥ 3, a molecular diagnosis was disclosed in about 45%. Among the remaining patients, we identified in 3 probands (1.7%) with UPD(20)mat (Mulchandani–Bhoj–Conlin syndrome, OMIM #617352), a molecular mechanism deregulating the GNAS locus and described in 21 cases, characterized by severe feeding difficulties associated with failure to thrive, preterm birth, and intrauterine/postnatal growth retardation. Our patients share prominent forehead, feeding difficulties, postnatal growth delay, and advanced maternal age. Their clinical assessment and molecular diagnostic flowchart contribute to better define the characteristics of this rare imprinting disorder and to rank UPD(20)mat as the fourth most common pathogenic molecular defect causative of SRS. MDPI 2021-04-17 /pmc/articles/PMC8073552/ /pubmed/33920573 http://dx.doi.org/10.3390/genes12040588 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tannorella, Pierpaola Minervino, Daniele Guzzetti, Sara Vimercati, Alessandro Calzari, Luciano Patti, Giuseppa Maghnie, Mohamad Allegri, Anna Elsa Maria Milani, Donatella Scuvera, Giulietta Mariani, Milena Modena, Piergiorgio Selicorni, Angelo Larizza, Lidia Russo, Silvia Maternal Uniparental Disomy of Chromosome 20 (UPD(20)mat) as Differential Diagnosis of Silver Russell Syndrome: Identification of Three New Cases |
title | Maternal Uniparental Disomy of Chromosome 20 (UPD(20)mat) as Differential Diagnosis of Silver Russell Syndrome: Identification of Three New Cases |
title_full | Maternal Uniparental Disomy of Chromosome 20 (UPD(20)mat) as Differential Diagnosis of Silver Russell Syndrome: Identification of Three New Cases |
title_fullStr | Maternal Uniparental Disomy of Chromosome 20 (UPD(20)mat) as Differential Diagnosis of Silver Russell Syndrome: Identification of Three New Cases |
title_full_unstemmed | Maternal Uniparental Disomy of Chromosome 20 (UPD(20)mat) as Differential Diagnosis of Silver Russell Syndrome: Identification of Three New Cases |
title_short | Maternal Uniparental Disomy of Chromosome 20 (UPD(20)mat) as Differential Diagnosis of Silver Russell Syndrome: Identification of Three New Cases |
title_sort | maternal uniparental disomy of chromosome 20 (upd(20)mat) as differential diagnosis of silver russell syndrome: identification of three new cases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073552/ https://www.ncbi.nlm.nih.gov/pubmed/33920573 http://dx.doi.org/10.3390/genes12040588 |
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