Maternal Uniparental Disomy of Chromosome 20 (UPD(20)mat) as Differential Diagnosis of Silver Russell Syndrome: Identification of Three New Cases.
Genes (Basel)
; 12(4)2021 04 17.
Article
em En
| MEDLINE
| ID: mdl-33920573
ABSTRACT
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/IGF2IG-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.
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Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 20
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Cromograninas
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Subunidades alfa Gs de Proteínas de Ligação ao GTP
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Dissomia Uniparental
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Síndrome de Silver-Russell
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Adult
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Child
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Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article