PMC8498701_01
Pedigree of the Chinese family segregating Woodhouse-Sakati syndrome (WSS) in an autosomal recessive manner. Male individuals are represented by squares, and females are represented by circles. Half-filled symbols represent a DCAF17 heterozygous mutation, while filled symbols represent a DCAF17 homozygous mutation. The third child of the patient's parents died at 7 mo and his genetic analyses could not be investigated.
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F1
The proband was a 25-yr-old woman, the first child of healthy first cousin parents (Figure 1), with a height of 156 cm and a body weight of 56 kg. In addition, generations I and II above the patient's parents died, and genetic analysis could not be performed (Figure 1). Her parent's and younger brother's samples were tested via Sanger sequencing for verification (Supplementary Figure S1).
Clinical manifestations of the proband. She presented with sparse hair, especially on both temporal sides and on the forehead, with a progeric face and a large forehead with prominent ears (A,B). Secondary sexual characteristics were incompletely developed (C,D).
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F2
Axillary or pubic hair was not present, and minimal breast budding was present with marked vulvar hypoplasia (Figure 2). With pathogenicity analysis, we detected the pathogenic locus (Supplementary Figure S2).
Pituitary MRI of the patient. T2-weighted MR imaging for the patient showed a partially empty sella and a small pituitary gland (arrow) (A); Magnetic sensitivity weighted imaging showed no abnormal iron deposition accumulation (B).
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F3
Magnetic resonance imaging (MRI) revealed a small pituitary, partially empty sella, no iron deposits in the globus pallidus, and multiple intracranial white matter hyperintensities that may be of vascular origin (Figure 3).
Sanger sequencing showed that the patient's (A) and her younger brother's (D)
DCAF17 harbored a homozygous mutation c.1111delA, p.(Ile371Term), while their father (B) and mother (C) were heterozygous for this mutation at this site.
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F4
The c.1111delA mutation is a nonsense mutation leading to a premature stop codon p.(Ile371Term) (Figure 4).