The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome

Am J Med Genet A. 2018 Feb;176(2):465-469. doi: 10.1002/ajmg.a.38581. Epub 2017 Dec 19.

Abstract

RNU4ATAC pathogenic variants to date have been associated with microcephalic osteodysplastic primordial dwarfism, type 1 and Roifman syndrome. Both conditions are clinically distinct skeletal dysplasias with microcephalic osteodysplastic primordial dwarfism, type 1 having a more severe phenotype than Roifman syndrome. Some of the overlapping features of the two conditions include developmental delay, microcephaly, and immune deficiency. The features also overlap with Lowry Wood syndrome, another rare but well-defined skeletal dysplasia for which the genetic etiology has not been identified. Characteristic features include multiple epiphyseal dysplasia and microcephaly. Here, we describe three patients with Lowry Wood syndrome with biallelic RNU4ATAC pathogenic variants. This report expands the phenotypic spectrum for biallelic RNU4ATAC disorder causing variants and is the first to establish the genetic cause for Lowry Wood syndrome.

Keywords: Lowry Wood syndrome; RNU4ATAC; epiphyseal dysplasia; microcephaly; skeletal dysplasia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / physiopathology
  • Child, Preschool
  • Developmental Disabilities / genetics
  • Developmental Disabilities / physiopathology
  • Dwarfism / genetics*
  • Dwarfism / physiopathology
  • Female
  • Fetal Growth Retardation / genetics
  • Fetal Growth Retardation / physiopathology
  • Growth Disorders / genetics*
  • Growth Disorders / physiopathology
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / physiopathology
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Male
  • Microcephaly / genetics*
  • Microcephaly / physiopathology
  • Mutation
  • Osteochondrodysplasias / genetics*
  • Osteochondrodysplasias / physiopathology
  • Phenotype
  • Primary Immunodeficiency Diseases
  • RNA, Small Nuclear / genetics*
  • Retinal Diseases / genetics*
  • Retinal Diseases / physiopathology
  • X-Linked Intellectual Disability / genetics*
  • X-Linked Intellectual Disability / physiopathology

Substances

  • RNA, Small Nuclear
  • RNU4ATAC RNA, human

Supplementary concepts

  • Lowry Wood syndrome
  • Roifman syndrome