Neonatal progeriod syndrome associated with biallelic truncating variants in POLR3A.

Document Type

Article

Publication Date

12-1-2016

Identifier

PMID: 27612211 DOI: 10.1002/ajmg.a.37960

Abstract

Wiedemann-Rautenstrauch syndrome, also known as neonatal progeroid syndrome, is a rare condition with fewer than 40 patients reported in the literature. Characteristic physical findings include neonatal progeroid appearance, sparse scalp hair, prominent scalp veins, and lipoatrophy; in addition, neonatal teeth are often a distinctive finding. The inheritance pattern of this disorder has been postulated to be autosomal recessive, although a specific gene has not been identified. Here we report an infant with the characteristic phenotypic features of Wiedemann-Rautenstrauch syndrome in whom exome sequencing identified two pathogenic variants in POLR3A: c.1909+18G>A; p.(Y637Cfs*23) and c.2617C>T; p.(R873*). Mutations in POLR3A (OMIM #614258) are associated with 4H leukodystrophy syndrome characterized by the triad of hypomyelination, hypodontia, and hypogonadotrophic hypogonadism. The present patient's genotype implies a broader phenotypic range for POLR3A mutations and might expand the clinical spectrum. This proband is notable because she had two null pathogenic variants. Replication in other patients clinically diagnosed with Wiedemann-Rautenstrauch syndrome is needed to further demonstrate this gene-disease association. © 2016 Wiley Periodicals, Inc.

Journal Title

American journal of medical genetics. Part A

Volume

170

Issue

12

First Page

3343

Last Page

3346

MeSH Keywords

Abnormalities, Multiple; Alleles; Amino Acid Substitution; Female; Fetal Growth Retardation; Genetic Association Studies; Genotype; Humans; Infant; Phenotype; Prenatal Diagnosis; Progeria; RNA Polymerase III; Sequence Deletion

Keywords

4H syndrome; POLR3A gene; Wiedemann-Rautenstrauch syndrome; leukodystrophy; neonatal progeriod syndrome

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