Genotypic and phenotypic analysis of an oculocutaneous albinism patient: a case report and review of the literature

Abstract

Background: Oculocutaneous albinism is a rare autosomal recessive disorder caused by congenital melanin deficiency, resulting in hypopigmentation of the eyes, hair, and skin. This study included a Chinese family with an oculocutaneous albinism pedigree, in which the proband presented with oculocutaneous albinismcombined with secondary angle closure, which has been rarely reported in previous literature. This article primarily focused on the clinical and genetic examination results of this patient and provided recommendations for ophthalmologist to treat patients with oculocutaneous albinism in clinical practice.

Case presentation: The proband in this case study is a 53-year-old Chinese male who showed depigmentation of the skin, hair, iris, and fundus, accompanied by photophobia, decreased vision, high intraocular pressure, nystagmus, macular fovea hypoplasia, and cataracts. Owing to the opacity and expansion of the lens, the volume ratio of lens to eyeball was increased, causing crowded anterior segment, bombed iris, and narrowed chamber angle and, ultimately, leading to secondary angle closure. Whole-exome sequencing suggested that the two patients in the pedigree harbored the compound heterozygous variants c.230G > A (p. Arg77Gln) and c.832G > A (p. Arg278*) in the TYR gene, while the healthy member carried the TYR c.230G > A (p. Arg77Gln) variant, which was consistent with the autosomal recessive inheritance pattern and further confirmed the diagnosis was oculocutaneous albinism. On the basis of the above results, the patient was diagnosed with oculocutaneous albinism, senile mature cataract, and secondary angle closure in the right eye and ocular hypertension in the left eye, as well as bilateral nystagmus. Then, the patient was prescribed carteolol eye drops to control intraocular pressure and underwent phacoemulsification and intraocular lens implantation surgery for the right eye. Postoperatively, the patient's intraocular pressure was effectively controlled, and visual acuity improved.

Conclusion: We report a patient with oculocutaneous albinism combined with cataract and secondary angle closure, and whole-exome sequencing suggested that he harbored TYR gene variants. Comprehensive examinations were important for identifying the causes of angle closure and making proper treatment strategies. Genetic testing enabled precise diagnosis and genetic counseling.

Keywords: TYR variant; Angle closure; Case report; Oculocutaneous albinism.

Fig. 1

The family tree. This family included two patients (II:2 and II:6). Patient II:6 is the proband

Fig. 2

Slit lamp examination and color fundus photography: in the right eye, the cornea was transparent, the anterior chamber was shallow, the pupil was round, with a diameter of about 3 mm and sensitive to light reflection, the iris was widely depigmented, and the lens appeared opaque and swollen, leading to poor visibility of the fundus (top and bottom left). In the left eye, the cornea was transparent, with deep anterior chamber and slightly cloudy lens (top right), and the fundus showed widespread depigmentation of the retina and choroid and large choroidal blood vessels (bottom right)

Fig. 3

Optical coherence tomography results of the left eye. Horizontal (left) and vertical (right) scanning images presented the hypoplasia of the macular fovea in the left eye

Fig. 4

Ultrasound biomicroscopy results. The anterior chamber of the right eye was shallow, with the central anterior chamber depth of 1.81 mm, and the chamber angle was narrow (left). The chamber angle of the left was open in all quadrants, and the depth of central anterior chamber was 2.71 mm (right)

Fig. 5

B-scan ultrasonography results. The axial length was 23.85 mm, and the thickness of the lens was 5.62 mm in the right eye (top and bottom left). The axial length was 26.51 mm and the thickness of the lens was 3.88 mm in the left eye (top and bottom right). The vitreouses of both eyes had punctate and mass echoes with high mobility, and no obvious abnormalities were observed in the retina and orbit

Fig. 6

Sanger sequencing results of the three subjects. Patient II:2 and II:6 harbored compound heterozygous variants c.230G > A (p. Arg77Gln) and c. 832G > A (p. Arg278*) in the TYR gene. The healthy member III:2 carried the heterozygous variant c.230G > A (p. Arg77Gln) in the TYR gene