PMC7273484_01
(a) Pedigree of the DA5D family with segregation analysis. The black symbols represent an affected member, and the arrow indicates the proband. Genotypes are identified by letters and slash, with red representing mutations. (b-f) The parts of phenotypes of the proband. (b) Facial features and contractures of the wrists, elbows, and knees in the proband. The proband had the bilateral distal arthrogryposis (c, d) and the webbing of bilateral fingers (e) and elbows (f).
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fig1
We identified a DA5D family from Hunan Province, China (Figure 1(a)). The patient had bilateral contractures of the fingers, wrist, elbow, and knees, without abnormal feet (Figures 1(b)-1(d)). Notably, he had webbing of the bilateral fingers and elbows (Figures 1(e) and 1(f)). He presented facial features, including left mild facial weakness, left ptosis, arched eyebrows, strabismus, protruding ears, and cleft palate (surgically repaired at the age of 3 years) (Figure 1(b)).
(a) Sequencing results of the ECEL1 mutations. Sequence chromatograms indicate compound heterozygosity (NM_004826: c.69C>A, p.C23* and c.1810G>A, p.G604R) in the family with DA5D. (b) The mutation sites (G604R) are highly evolutionarily conserved across species. The red graph represents mutated amino acids, and the red box emphasizes these sites across species for comparison.
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fig2
Sanger sequencing showed that the novel nonsense mutation (c.69C>A, p.C23*) of ECEL1 in the patient was inherited from his mother, and another mutation (c.1810G>A, p.G604R) was from his father; each cosegregated with the affected family member (Figure 2(a)). Additionally, the amino acid sequence alignment analysis suggested that the mutation (c.1810G>A, p.G604R) was located in a highly evolutionarily conserved site (Figure 2(b)).