PMC5732153_01
(A,B) Family tree and sequence chromatogram. The heterozygous KMT2D mutation L3564V was identified in the proband (II.2). The same mutation was not found in her parents (I.1 and I.2), suggesting that it was a de novo mutation. (C) Patient growth curve. Severe growth failure was improved by the introduction of growth hormone and levothyroxine. Three years after starting growth hormone therapy, insulin therapy was started to treat diabetes associated with insulin insufficiency. (D) Photographs of the face, ears, and hands at age 24 years. (Left) The patient had right facial nerve palsy, and a broad and depressed nasal tip. Her long eyelids with eversion of the lateral third of the lower eyelid, which is a typical finding of Kabuki syndrome, are not obvious in the photograph. (Top right) Abnormality of the external ear. Large prominent earlobes, which are a typical finding of Kabuki syndrome, were absent. (Bottom right) No abnormalities of the fingertip pads or the hockey-stick palmar crease were observed.
fgene-08-00210-g001.jpg
PMC5732153_02_fgene-08-00210-g001.jpg
F1
The patient is currently 24 years old and has multiple dysmorphic features (Figure 1D). TruSight One sequencing panel (Illumina, San Diego, CA, United States) revealed a novel heterozygous mutation, c.10690 C > G (p.L3564V), in KMT2D. The mutation was confirmed by Sanger sequencing (Figure 1B).
(A-C) Computed tomography findings at age 11 years. (A) Hypoplasia of the pancreatic body and tail (yellow arrow). (B) Uterine hypoplasia (yellow arrow) was identified before estrogen replacement therapy. (C) Computed tomography finding of the internal ear. (Upper images) Aplasia of both posterior semicircular canals (yellow circles). (Lower images) The presence of anterior and lateral semicircular canals was confirmed (yellow arrows). (D) Magnetic resonance imaging showing empty sella.
fgene-08-00210-g002.jpg
PMC5732153_01_fgene-08-00210-g002.jpg
F2
Computed tomography revealed hypoplasia of the pancreatic body and tail (Figure 2A), and severe uterine hypoplasia with the presence of both ovaries (Figure 2B). It also revealed bilateral atresia of the external auditory meatus, hypoplasia of the right vestibular aqueduct, bilateral hypoplasia of the long limb of incus, and bilateral agenesis of stapes and the posterior semicircular canal (Figure 2C). Magnetic resonance imaging of the brain showed an empty sella (Figure 2D).
PMC5732153_02
(A,B) Family tree and sequence chromatogram. The heterozygous KMT2D mutation L3564V was identified in the proband (II.2). The same mutation was not found in her parents (I.1 and I.2), suggesting that it was a de novo mutation. (C) Patient growth curve. Severe growth failure was improved by the introduction of growth hormone and levothyroxine. Three years after starting growth hormone therapy, insulin therapy was started to treat diabetes associated with insulin insufficiency. (D) Photographs of the face, ears, and hands at age 24 years. (Left) The patient had right facial nerve palsy, and a broad and depressed nasal tip. Her long eyelids with eversion of the lateral third of the lower eyelid, which is a typical finding of Kabuki syndrome, are not obvious in the photograph. (Top right) Abnormality of the external ear. Large prominent earlobes, which are a typical finding of Kabuki syndrome, were absent. (Bottom right) No abnormalities of the fingertip pads or the hockey-stick palmar crease were observed.
fgene-08-00210-g001.jpg
PMC5732153_02_fgene-08-00210-g001.jpg
F1
The patient is currently 24 years old and has multiple dysmorphic features (Figure 1D). TruSight One sequencing panel (Illumina, San Diego, CA, United States) revealed a novel heterozygous mutation, c.10690 C > G (p.L3564V), in KMT2D. The mutation was confirmed by Sanger sequencing (Figure 1B).