TUBB4B gene mutation in Leber phenotype of congenital amaurosis syndrome associated with early-onset deafness

Anita Maasz; Kinga Hadzsiev; Reka Ripszam; Anna Zsigmond; Erika Maka; Krisztina Knezy; Balazs Lesch; Adrienn Nemeth; Judit Bene; Bence Galik; Attila Gyenesei; Bela Melegh

doi:10.1016/j.ejmg.2022.104471

TUBB4B gene mutation in Leber phenotype of congenital amaurosis syndrome associated with early-onset deafness

Eur J Med Genet. 2022 Apr;65(4):104471. doi: 10.1016/j.ejmg.2022.104471. Epub 2022 Feb 28.

Authors

Affiliations

¹ Department of Medical Genetics, Clinical Centre and Medical School, University of Pecs, Pecs, H-7624, Hungary; Szentagothai Research Centre, Clinical Genetics and Genomics Research Group, University of Pecs, Pecs, H-7624, Hungary. Electronic address: [email protected].
² Department of Medical Genetics, Clinical Centre and Medical School, University of Pecs, Pecs, H-7624, Hungary; Szentagothai Research Centre, Clinical Genetics and Genomics Research Group, University of Pecs, Pecs, H-7624, Hungary.
³ Department of Ophthalmology, Semmelweis University, Budapest, H-1085, Hungary.
⁴ Department of Otorhinolaryngology, Clinical Centre and Medical School, University of Pecs, Pecs, H-7624, Hungary.
⁵ Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, University of Pecs, Pecs, H-7624, Hungary.

PMID: 35240325
DOI: 10.1016/j.ejmg.2022.104471

Abstract

Beta-tubulin 4B isotype is one of the subunits of microtubules encoded by TUBB4B gene on chromosome 9, which is responsible for the maintenance of microtubule stability. In humans, mutations in microtubule-encoding genes have been associated with several tubulinopathies with very heterogeneous symptoms. So far, only two missense mutations in TUBB4B gene have been found to have pathological implications in this disorder. Here we report a Hungarian family with three affected members, mother and her 12- and 14-year-old children, who suffer from ophthalmologic and hearing impairments probably due to c.1171C > T missense variant in the TUBB4B gene. The presented case is the second report, and unique in the literature because of three affected family members carrying the same mutation and the family provides evidence for a quite similar but not identical phenotype of LCAEOD in subjects carrying this mutation.

Keywords: LCAEOD; Leber congenital amaurosis syndrome; NGS; Sensorineural hearing loss; TUBB4B.

MeSH terms

Blindness
Deafness* / genetics
Female
Humans
Leber Congenital Amaurosis* / genetics
Mutation
Pedigree
Phenotype
Tubulin* / genetics

Substances

TUBB4B protein, human
Tubulin