Hermansky-Pudlak syndrome type 2: A rare cause of severe periodontitis in adolescents-A case study

Abstract

Background and aims: Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism (OCA) and platelet storage pool deficiency. The HPS-2 subtype is distinguished by neutropenia, and little is known about its periodontal phenotype in adolescents. AP3B1 is the causative gene for HPS-2. A 13-year-old Chinese girl presented to our department suffering from gingival bleeding and tooth mobility. Her dental history was otherwise unremarkable. Suspecting some systemic diseases as the underlying cause, the patient was referred for medical consultation, a series of blood tests, and genetic tests. In this case study, periodontal status and mutation screening of one HPS-2 case are presented.

Methods: Blood analysis including a complete blood count (CBC) and glycated hemoglobin levels were measured. Platelet transmission electron microscopy (PTEM) was performed to observe the dense granules in platelets. Whole-exome sequencing (WES) and Sanger sequencing were performed to confirm the pathogenic variants.

Results: A medical diagnosis of HPS-2 was assigned to the patient. Following the medical diagnosis, a periodontal diagnosis of "periodontitis as a manifestation of systemic disease" was assigned to the patient. We identified novel compound heterozygous variants in AP3B1 (NM_003664.4: exon7: c.763C>T: p.Q255^*) and (NM_003664.4: exon1: c.53_56dup: p.E19Dfs^*21) in this Chinese pedigree with HPS-2.

Conclusion: This case study indicates the importance of periodontitis as a possible indicator of underlying systemic disease. Systemic disease screening is needed when a young patient presents with unusual, severe periodontitis, as the oral condition may be the first of a systemic abnormality. Our work also expands the spectrum of AP3B1 mutations and further provides additional genetic testing information for other HPS-2 patients.

Keywords: Hermansky-Pudlak syndrome type 2 (HPS-2); adaptor protein complex 3 (AP3B1); genetics; juvenile; periodontitis.

Figure 1

Intraoral and facial photo (July 12, 2021): (A–I) The gums were extensively red and swollen. Abduction and displacement of maxillary anterior teeth. (J) The proband has blonde hair and whole-body skin whiteness.

Figure 2

The proband's periodontal chart at the initial consultation.

Figure 3

(A) Panoramic radiograph of the proband. (B–D) 3D Volumetric reconstructive cone-beam computed tomographic (CBCT) images of the whole mouth from different directions. (E–G) Alveolar bones of teeth #12, #11, and #26 were absorbed to the root apex.

Figure 4

(A–D) Morphological analysis of platelets by platelet transmission electron microscopy (PTEM) shows multiple empty sacks (yellow arrows) in the proband's platelets without dense granules. Occasionally, abnormally dense granules with irregular shapes, decreased the content density and increased clear space (blue arrow). The platelet lysosomes (red arrow) increase in volume. Indicated magnification: (A) 10kx, (B) 10kx, (C) 30kx, (D) 20kx.

Figure 5

(A) The pedigree contains three family members and two generations of Hermansky-Pudlak syndrome type 2 (HPS-2) (I1, I2, II1). The square represents the male, and the circle represents the female. The filled circle (arrow) represents the proband. A half-filled square or circle represents the carrier. (B) Sequence Chromatograms show the compound heterozygous mutations (c.763C>T: p.Q255*) and (c.53_56dup: p.E19Dfs*21) in the AP3B1 gene.