case_images: PMC10679387_01
case_images: Masculine features and Abdominal CT scan of patient. (A) Abdominal CT scan showed bilateral adrenal hyperplasia, with a nodule on the right approximately 27x22mm and a nodule on the left approximately 42x28mm. (B) Abdominal CT scan revealed recurrence of the right adrenal gland hyperplasia two years after surgery. (C) Physical examination revealed greasy skin pigmentation, facial acne, and slight mustache on the upper lip.
case_images: fendo-14-1216767-g001.jpg
case_images: PMC10679387_02_fendo-14-1216767-g001.jpg
case_images: f1
case_images: Abdominal-enhanced CT scan showed structural disorder in the right adrenal gland area, with spotted and striped shadows (Figure 1B). Physical examination revealed greasy skin pigmentation, facial acne, and slight mustache on the upper lip (Figure 1C).
case_images: PMC10679387_02
case_images: Masculine features and Abdominal CT scan of patient. (A) Abdominal CT scan showed bilateral adrenal hyperplasia, with a nodule on the right approximately 27x22mm and a nodule on the left approximately 42x28mm. (B) Abdominal CT scan revealed recurrence of the right adrenal gland hyperplasia two years after surgery. (C) Physical examination revealed greasy skin pigmentation, facial acne, and slight mustache on the upper lip.
case_images: fendo-14-1216767-g001.jpg
case_images: PMC10679387_02_fendo-14-1216767-g001.jpg
case_images: f1
case_images: Abdominal-enhanced CT scan showed structural disorder in the right adrenal gland area, with spotted and striped shadows (Figure 1B). Physical examination revealed greasy skin pigmentation, facial acne, and slight mustache on the upper lip (Figure 1C).
case_images: PMC10679387_03
case_images: p.Val68Gly of the CYP11B1 in patient. (A) Visualization of variant in CYP11B1 using IGV. Apparently, the patient was a homozygous variant, c.203T>G, located in exon 1. (B) The sequencing chromatogram of the variant in CYP11B1. Arrow indicates mutant nucleotide (c.203T>G). (C) Conservation prediction of this mutant amino acid among different species. (D) Three-dimensional structure of wild-type CYP11B1 and mutant-type CYP11B1. The yellow dotted line represents hydrogen bond.
case_images: fendo-14-1216767-g002.jpg
case_images: PMC10679387_03_fendo-14-1216767-g002.jpg
case_images: f2
case_images: Initially, a novel homozygous missense variant in CYP11B1, NM_000497.4: c.203T>G (p.Val68Gly) was identified (Figure 2A). Then the variant was further confirmed by sanger sequencing (Figure 2B; Supplementary Materials and Methods). Multiple alignments of CYP11B1 suggest that the amino acidic residue, Val68, is conserved at this position across various species (Figure 2C). The prediction of protein three-dimensional structure revealed that Val68 residue locates in an alpha-helix, and p.Val68Gly causes a change in hydrogen bond length, which may lead to alterations in protein conformation and stability (Figure 2D).
case_images: The chimeric CYP11B2/CYP11B1 gene in patient. (A) The deletion covering exons 1-6 of CYP11B1 and exons 7-9 in CYP11B2 by whole exome sequencing. The violin plot illustrates the distribution of sequencing depth for normal reference samples on each exon, with the ordinate is the Z-score standardization for the sequencing depth. The dotted lines in different colors represent the maximum, average, median and minimum of sequencing depth Z-score in normal references. Solid line represents the sequencing depth Z-score of CYP11B1 and CYP11B2 in the proband sample. Specifically, the sequencing depth Z-score in exons 7-9 of CYP11B2 and exon 1-6 of CYP11B1 is lower than the minimum value in the normal references. (B) Schematic representation of the CYP11B2 gene (exons displayed as grey boxes) and the CYP11B1 gene (exons displayed as white boxes). In the investigated patient, the CYP11B2/CYP11B1 chimera consisting of the promoter and exons 1-6 of CYP11B2 and exons 7-9 of CYP11B1. Arrows indicate the position of the 8 specific probes of CNVplex.(C) Graphic report of CNVplex result in the patient and control. Deletion occurred in the position of seven probes, except for the position of the last probe (located in the intron 2 of CYP11B2).
case_images: fendo-14-1216767-g003.jpg
case_images: PMC10679387_03_fendo-14-1216767-g003.jpg
case_images: f3
case_images: The deletion covers exon 1 to exon 6 of CYP11B1 and exon 7 to exon 9 of CYP11B2 (Figure 3A), resulting in the formation of a single hybrid gene consisting of the promoter and exons 1-6 of CYP11B2 and exons 7-9 of CYP11B1 (Figure 3B). Table 1), while the other probe showed a normal copy number outside of the potential deletion region (Figure 3C). This result confirmed the reliability of this deletion recognized by WES-CNV analysis.