Redefining the progeroid form of ehlers–danlos syndrome: Report of the fourth patient with B4GALT7 deficiency and review of the literature. Issue 10 (16th August 2013)

• Record Type: Journal Article
• Authors: Guo, Michael H.; Stoler, Joan; Lui, Julian; Nilsson, Ola; Bianchi, Diana W.; Hirschhorn, Joel N.; Dauber, Andrew
• Is Part Of: American journal of medical genetics. Volume 161:Issue 10(2013:Oct.)
• Page Start: 2519
• Page End: 2527
• Publication Date: 2013-08-16
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36128
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="ajmga36128-sec-0001" sec-type="section"> <p>Proteoglycans are a component of the extracellular matrix and are critical for cellular and tissue function. Mutations in proteoglycan components and enzymes involved in proteoglycan synthesis have been implicated in several growth disorders, with common features including short stature and skeletal dysplasia. For example, mutations in <italic>B4GALT7</italic>, a gene whose protein product catalyzes proteoglycan synthesis, have been associated with the rare progeroid variant of Ehlers–Danlos syndrome. Here, we conducted exome sequencing in a patient with a previously undiagnosed growth disorder and identified compound heterozygous mutations in <italic>B4GALT7</italic>. This patient is just the fourth individual with genetically confirmed progeroid variant of Ehlers–Danlos syndrome. The mutations include a previously characterized c.808C>T p.Arg270Cys substitution, and a novel c.122T>C p.Leu41Pro substitution. We demonstrate that the novel mutation caused decreased levels of the enzyme, supporting the pathogenicity of the mutation. Our report identifies a novel mutation in <italic>B4GALT7</italic> causing the progeroid variant of Ehlers–Danlos syndrome and contributes an extensive phenotypic characterization of a patient with the syndrome. We also reviewed the previous literature in addition to the present patient, and conclude that the key features associated with <italic>B4GALT7</italic> deficiency are short stature, developmental anomalies of the forearm bones and elbow, and bowing of the extremities, in addition to the classic features of Ehlers–Danlos syndrome. This report helps define the phenotype of the progeroid variant of Ehlers–Danlos syndrome and furthers our understanding of the effect of proteoglycan defects in growth disorders. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>