Tietz/Waardenburg type 2A syndrome associated with posterior microphthalmos in two unrelated patients with novel MITF gene mutations.
Tietz syndrome and Waardenburg syndrome type 2A are allelic conditions caused by MITF mutations. Tietz syndrome is inherited in an autosomal dominant pattern and is characterized by congenital deafness and generalized skin, hair, and eye hypopigmentation, while Waardenburg syndrome type 2A typically includes variable degrees of sensorineural hearing loss and patches of de-pigmented skin, hair, and irides. In this paper, we report two unrelated families with MITF mutations. The first family showed an autosomal dominant pattern and variable expressivity. The second patient was isolated. MITF gene analysis in the first family demonstrated a c.648A>C heterozygous mutation in exon 8 c.648A>C; p. (R216S), while in the isolated patient, an apparently de novo heterozygous c.1183_1184insG truncating mutation was demonstrated in exon 10. All patients except one had bilateral reduced ocular anteroposterior axial length and a high hyperopic refractive error corresponding to posterior microphthalmos, features that have not been described as part of the disease. Our results suggest that posterior microphthalmos might be part of the clinical characteristics of Tietz/Waardenburg syndrome type 2A and expand both the clinical and molecular spectrum of the disease. © 2016 Wiley Periodicals, Inc.
Department of Genetics, Hospital "Dr. Luis Sánchez Bulnes", Asociación para Evitar la Ceguera en México, Mexico City, Mexico.
Vianney
V
Cortés-González
Department of Biochemistry, National Autonomous University of Mexico, Mexico City, Mexico.|Research Unit and Genetics Department, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.
Juan Carlos
JC
Zenteno
Ophthalmology, Hospital "Dr. Luis Sánchez Bulnes", Asociación para Evitar la Ceguera en México, Mexico City, Mexico.
Martín
M
Guzmán-Sánchez
Department of Retina, Hospital "Dr. Luis Sánchez Bulnes", Asociación para Evitar la Ceguera en México, Mexico City, Mexico.
Verónica
V
Giordano-Herrera
Research Unit and Genetics Department, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.
Dalia
D
Guadarrama-Vallejo
Department of Cornea, Hospital "Dr. Luis Sánchez Bulnes", Asociación para Evitar la Ceguera en México, Mexico City, Mexico.
Narlly
N
Ruíz-Quintero
Department of Genetics, Hospital "Dr. Luis Sánchez Bulnes", Asociación para Evitar la Ceguera en México, Mexico City, Mexico.
Cristina
C
Villanueva-Mendoza
D000483:Alleles; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D005091:Exons; D019066:Facies; D006579:Heterozygote; D006801:Humans; D008297:Male; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D008850:Microphthalmos / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D010808:Physical Examination; D014849:Waardenburg Syndrome / Q000175:diagnosis / Q000235:genetics*
D051739:Microphthalmia-Associated Transcription Factor
MITF; Tietz syndrome; Waardenburg syndrome type 2A; congenital deafness; posterior microphthalmos