Haploinsufficiency of BMP4 gene may be the underlying cause of Frías syndrome. Issue 2 (5th December 2013)

• Record Type: Journal Article
• Authors: Martínez‐Fernández, María Luisa; Bermejo‐Sánchez, Eva; Fernández, Belén; MacDonald, Alexandra; Fernández‐Toral, Joaquín; Martínez‐Frías, María Luisa
• Is Part Of: American journal of medical genetics. Volume 164:Issue 2(2014.)
• Page Start: 338
• Page End: 345
• Publication Date: 2013-12-05
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36224
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="ajmga36224-sec-0001" sec-type="section"> <p>In 2005, we reported on a family as having Frías syndrome (OMIM: 609640), with four affected members displaying a pattern of congenital defects nearly identical to those observed in a mother and son described by Frias [Frías et al. (1975). <italic>Birth Defects Orig Artic Ser</italic> 11:30–33]. These defects included growth deficiency, facial anomalies, and hand and foot alterations. We had the opportunity to study this family again due to the birth of another affected girl, who presented with similar facial characteristics to those of her elder half‐sister and the rest of affected relatives, which consisted of mild exophthalmia, bilateral palpebral ptosis, downslanting palpebral fissures, and hypertelorism. We performed array‐CGH, which identified an identical interstitial deletion of chromosome 14q22.1–q22.3 in the mother and two daughters. The deletion is 4.06 Mb in length and includes the <italic>BMP4</italic> gene, a member of the bone morphogenetic protein (BMP) family of secreted proteins. A review of the literature showed that deletions or mutations of this gene underlie congenital defects affecting brain, eye, teeth, and digit development. Although the clinical manifestations of the current family correlate with the defects observed in patients having either 14q22–q23 deletions or mutations of <italic>BMP4</italic>, they show a milder phenotype. In order to understand the clinical variability, we evaluated the already known functional characteristics of the <italic>BMP</italic> gene members. This gene family plays an important role during early embryogenesis, and the complex synergistic functions and redundancies of the BMPs led us to conclude that haploinsufficiency of <italic>BMP4</italic> is likely to be responsible for the clinical expression of Frías syndrome. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>