ORIGINAL ARTICLE Ocular albinism with infertility and late-onset sensorineural hearing loss Bjørn K. Fabian-Jessing 1,2 | Else Marie Vestergaard 3 | Astrid S. Plomp 4 | Arthur A. Bergen 4 | Wouter A. Dreschler 5 | Morten Duno 6 | Beata S. Winiarska 7 | Linda Neumann 7 | Michael Gaihede 2,8 | Henrik Vorum 7 | Michael B. Petersen 1,2 1 Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark 2 Department of Clinical Medicine, Aalborg University, Aalborg, Denmark 3 Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark 4 Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands 5 Department of Otorhinolaryngology Head and Neck Surgery, Academic Medical Center, Amsterdam, The Netherlands 6 Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark 7 Department of Ophthalmology, Aalborg University Hospital, Aalborg, Denmark 8 Department of Otolaryngology, Head and Neck Surgery, Aalborg University Hospital, Aalborg, Denmark Correspondence Bjørn K. Fabian-Jessing, Department of Clinical Genetics, Aalborg University Hospi- tal, Ladegårdsgade 5, Bygning E, 5. etage, Aalborg 9000, Denmark. Email: b.fabianjessing@rn.dk Ocular albinism type 1 (OA1) is caused by mutations in the GPR143 gene located at Xp22.2. The manifestations, which are due to hypopigmentation, are confined to the eyes and optic pathway. OA1 associated with late-onset sensorineural hearing loss was previously reported in a single fam- ily and hypothesized to be caused by a contiguous gene deletion syndrome involving GPR143 and the adjacent gene, TBL1X. Here, we report on a family with OA1, infertility, late-onset sensorineu- ral hearing loss, and a small interstitial Xp microdeletion including the GPR143, TBL1X, and SHROOM2 genes. In addition, we re-examined a patient previously described with OA1, infertility and a similar Xp deletion with audiologic follow-up showing a late-onset sensorineural hearing loss. Our results raise an intriguing question about the possibility for TBL1X (absence) involvement in this type of hearing loss. However, our study cannot claim a causative relationship and more convincing evidence is needed before the hypothesis can be accepted that TBL1X could be involved in late-onset sensorineural hearing loss and that ocular albinism with late-onset sensori- neural hearing loss can present itself as a contiguous gene deletion/microdeletion syndrome. The finding of infertility in all affected male patients demonstrates that this deletion, including the SHROOM2 gene, may be a potentially causative X-linked genetic factor of male infertility. KEYWORDS albinism, ocular albinism, OA1, GPR143, hearing loss, TBL1X, male infertility, oligozoospermia, asthenozoospermia, X chromosome, SHROOM2, contiguous gene deletion syndrome 1 | INTRODUCTION Albinism is the clinical term for inherited disorders of hypopigmentation caused by defects in melanin synthesis. Albinism is mainly subdivided into oculocutaneous albinism, affecting the skin, hair, eyes and optic pathway and ocular albinism, where symptoms are confined to the eyes and optic pathway (King et al., 2007). Ocular albinism type 1 (OA1; OMIM 300500), also known as the Nettleship-Falls type, is the most common type of ocular albinism with an estimated prevalence of 1/60,000 (Rosenberg & Schwartz, 1998). OA1 is an X-linked trait caused by mutations in the GPR143 gene located at Xp22.2. The gene encodes G protein-coupled receptor 143—an inte- gral membrane protein specifically expressed by melanocytes and retinal pigment epithelium (Bassi et al., 1995; Schiaffino et al., 1999). Affected males display considerable phenotypic variability including reduced visual acuity, refractive errors, nystagmus, strabismus, absent or reduced stereo- psis, iris translucency, photophobia, optic disc abnormalities, foveal hypo- plasia, retinal hypopigmentation, and chiasmal misrouting of the optic nerves. The pigmentation of skin and hair generally appears normal, but histologic examination shows large melanosomes in the melanocytes (Charles et al., 1993; King et al., 2007). Female carriers can usually be identified by some degree of iris translucency and a characteristic mosaic pattern of retinal pigmentation due to random X-inactivation. Female car- riers with more advanced ocular manifestations due to skewed X- inactivation, such as reduced visual acuity and nystagmus, have been reported (Charles et al., 1992; Wuthisiri, Lingao, Capasso, & Levin, 2013). Am J Med Genet Part A. 2018;176A:1587–1593. wileyonlinelibrary.com/journal/ajmga V C 2018 Wiley Periodicals, Inc. | 1587 Received: 3 October 2014 | Revised: 30 January 2018 | Accepted: 13 February 2018 DOI: 10.1002/ajmg.a.38836