Mutations in HYAL2, Encoding Hyaluronidase 2, Cause a Syndrome of Orofacial Clefting and Cor Triatriatum Sinister in Humans and Mice - Fig 2

Micro-CT images of the skulls of Hyal2-/-and Hyal2+/-mice, transthoracic echocardiography images of Amish individuals homozygous for HYAL2 mutation c.443A>G, cardiac analysis in Hyal2-/-and Hyal2+/+mice (A) 3D Images of Hyal2-/- mice that died at P1, and the control (Hyal2+/-) which was sacrificed at P2, were created using CTvox software. All images were scanned and reconstructed using identical parameters and the dynamic range for the grey scale was held constant (i and ii). Dorsal views from the rostral end of the skull were prepared using a transfer function that colorized the grey scale such that areas of the bone with lower density are red (see density scale in image). (iii and iv). Ventral grey scale views of the skulls without the lower jaw. (v and vi). Space filled images of the vomer. * indicates the vomer head. Similar findings were evident in three additional Hyal2-/- mice found dead at P1. These images are not to scale. E, ethmoid; V, vomer; PS, presphenoid; BS, basisphenoid; PM, premaxilla; MA, maxilla; PA, palantine. (B) (i & ii) Apical 4-chamber image of the heart is shown with right atrium (RA), left atrium (LA), right ventricle (RV), and left ventricle (LV) labelled. Presence of membranous tissue (*) in the LA of Hyal2-/- mouse representing cor triatriatum sinister. (C) (i) Apical four chamber view of Amish individual XII:3: arrow indicates the membrane across the left atrium dividing the pulmonary venous confluence from the body of the left atrium (cor triatriatum sinister). (ii) Apical three chamber view with color. Doppler of individual XII:3: arrow indicates the anterior fenestration in the membrane dividing the left atrium, the laminar flow through the fenestration implies the non-obstructive nature of the membrane. (iii) Apical two chamber view of individual XII:9: arrow indicates the dilated coronary sinus indicative of a persistent left superior vena cava; RV: right ventricle, RA: right atrium, LV: left ventricle, LA: left atrium, CS: coronary sinus.