Novel PDE6B Mutation Presenting with Retinitis Pigmentosa – A Case Series of Three Patients

Abstract

Background Retinitis pigmentosa (RP) affects 2.5 million people worldwide. Increased identification of causative gene defects and the increasing possibility of treatment necessitates better knowledge of phenotype-genotype correlations to help identify patients who would benefit from targeted gene therapy and improve patientsʼ care. Here, we report on three RP patients with mutations in the PDE6Β Gene that have not been described previously.

History and Signs Three patients with a PDE6Β mutation were identified: 1. A 30-year-old male with a homozygotous mutation (c.[2351dupA],[2351dupA], p.[Q785Gfs*20],[Q785Gfs*20]) who was followed for 8 years. 2. A 54-year-old Caucasian woman with a heterozygous mutation [p.(K611Nfs*6), p.(Q567*)] who was followed for 40 years. 3. A 46-year-old Caucasian male [p.(E271K), p.(R627_E631del)]. All had noted an onset in childhood and complained of night blindness and photophobia. Typical bone spiculae were seen, and peripheral visual fields were progressively affected in all patients. Ganzfeld-ERG showed typical signs of rod-cone dystrophy. Patients 1 and 2 underwent cataract surgery at ages 27 and 36 years with an improvement in vision, while patient 3 had not developed a cataract at age 54.

Conclusions In children complaining of night blindness, a PDE6Β-associated RP needs to be taken into consideration. Apart from helping patients with optical aids, such as polarizing filters or magnification, a specific diagnosis is especially important in view of emerging genetic treatment options. In particular, in RP patients with a PDE6Β mutation, a phase I/II study is currently ongoing (https://clinicaltrials.gov/ct2/show/NCT03328130).

Zusammenfassung

Hintergrund Retinitis pigmentosa (RP) betrifft weltweit 2,5 Millionen Menschen. Die zunehmende Identifizierung ursächlicher Gendefekte und die zunehmende Möglichkeit der Behandlung erfordern bessere Kenntnisse der Phänotyp-Genotyp-Korrelationen, um Patienten zu identifizieren, die von einer gezielten Gentherapie profitieren würden, und um die Versorgung der Patienten zu verbessern. Hier berichten wir über 3 RP-Patienten mit Mutationen im PDE6Β-Gen, die bisher nicht beschrieben wurden.

Patienten und Methoden Drei Patienten mit einer PDE6Β-Mutation wurden identifiziert: 1. Ein 30 Jahre alter Mann mit einer homozygoten Mutation (c.[2351dupA],[2351dupA]; p.[Q785Gfs*20],[Q785Gfs*20]) wurde 8 Jahre lang beobachtet. 2. Eine 54-jährige kaukasische Frau mit einer heterozygoten Mutation (p.[K611Nfs*6],p.[Q567*]) wurde 40 Jahre betreut. 3. Ein 46 Jahre alter junger Mann (S.[E271K], S.[R627_E631del]). Alle bemerkten einen Beginn in der Kindheit und klagten über Nachtblindheit und Photophobie. Typische Knochenkörperchen und progrediente periphere Gesichtsfelder wurden bei allen Patienten beobachtet. Das Ganzfeld-ERG zeigte typische Anzeichen einer Stäbchen-Zapfen-Dystrophie. Bei den Patienten 1 und 2 wurde im Alter von 27 und 36 Jahren eine Kataraktoperation durchgeführt, die zu einer Verbesserung des Sehvermögens führte. Patient 3 hatte im Alter von 54 Jahren noch keine Katarakt entwickelt.

Schlussfolgerungen Bei Kindern, die sich über Nachtblindheit beschweren, muss eine PDE6Β-assoziierte RP in Betracht gezogen werden. Neben der Unterstützung durch optische Hilfsmittel wie Polarisationsfilter oder Vergrößerungshilfen ist insbesondere im Hinblick auf neu aufkommende genetische Behandlungsmöglichkeiten eine spezifische Diagnostik wichtig. Bei RP-Patienten mit einer PDE6Β-Mutation wird derzeit eine Phase-I/II-Studie durchgeführt (https://clinicaltrials.gov/ct2/show/NCT03328130).

Key words

retina - electrophysiology - genetics - PDE6B - retinitis pigmentosa - phenotype - genotype - novel mutation

Schlüsselwörter

Genetik - PDE6Β - Retinitis pigmentosa - Phänotyp - Genotyp - neue Mutation - Elektrophysiologie

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