MITF p.Arg217Thr Variant Identified in a Han Chinese Family with Tietz/Waardenburg Syndrome

Abstract

Waardenburg syndrome (WS) is a group of rare genetic disorders characterized by hearing loss, changes in coloring of hair, skin, and eyes, and alterations in the shape of the face. Tietz syndrome is another rare disorder which presented similar phenotypes to WS. Patients with Tietz/Waardenburg syndrome often present with pale blue eyes, albino skin, and distinctive hair coloring, such as a patch of white hair or hair that prematurely turns gray. At present, more than six candidate genes are responsible for four types of Waardenburg syndrome and Tietz syndrome. This study is aimed at identifying the pathogenic gene variants in a three-generation Han Chinese family with hearing loss, blue-gray iris, albino skin, and white hair. In order to discover the molecular genetic lesion underlying the disease phenotype, whole exome sequencing in the proband, with Tietz/Waardenburg syndrome phenotypes, of a Han Chinese family from HeBei, China, was conducted. A novel heterozygous c.650G>C/p.Arg217Thr variant in melanocyte inducing transcription factor (MITF) was identified. Sanger sequencing further validated that this mutation existed in three affected individuals and absent in healthy family members. Bioinformatics analysis predicted that this mutation was deleterious. Our study further identified the genetic lesion of the family. Simultaneously, our study may also contribute to genetic counseling, embryonic screening of in vitro fertilized embryos, and prenatal genetic diagnosis of patients with Tietz/Waardenburg syndrome, especially for the proband, unmarried and unpregnant women, to reduce familial transmission in this Han Chinese family.

The Tietz syndrome associated with cardiac malformation: a case report with literature review

“…The typical inherited pattern of Tietz syndrome is autosomal dominant [1,[4][5][6]. At the chromosome level this syndrome is associated with a nontruncating mutation in the basic domain of melanocyte inducing transcription factor (MITF) gene [1,8].…”

“…The typical inherited pattern of Tietz syndrome is autosomal dominant [1,[4][5][6]. At the chromosome level this syndrome is associated with a nontruncating mutation in the basic domain of melanocyte inducing transcription factor (MITF) gene [1,8]. The human MITF is located on chromosome 3p13, and it consists of 10 exons, spanning approximately 22.8 kilobases (kb) [1].…”

“…At the chromosome level this syndrome is associated with a nontruncating mutation in the basic domain of melanocyte inducing transcription factor (MITF) gene [1,8]. The human MITF is located on chromosome 3p13, and it consists of 10 exons, spanning approximately 22.8 kilobases (kb) [1]. This gene enables the synthesis of a protein called melanocyte inducing transcription factor (MITF) which helps control the development and function of melanocytes [1,2,8].…”

“…The human MITF is located on chromosome 3p13, and it consists of 10 exons, spanning approximately 22.8 kilobases (kb) [1]. This gene enables the synthesis of a protein called melanocyte inducing transcription factor (MITF) which helps control the development and function of melanocytes [1,2,8]. The production of melanin in melanocytes contributes to the color of hair, eyes, and skin.…”

“…It is an autosomal dominant syndrome due to a mutation in the melanocyte inducing transcription factor (MITF) gene which controls melanin biosynthesis in the melanocytes and contributes to the color of hair, eyes, and skin. The melanocytes are found in the inner ear where it plays an important role in hearing and MITF gene mutation contributes to bilateral sensorineural hearing loss [1,2]. The presence of melanocytes in the heart has been proven in mice and the expression of MITF in the heart is also high [3].…”