Chinese /IN
400-6006223
Disease Introduction
Usher syndrome is a common condition characterized by deafness and progressive visual lossChromosomal recessive genetic disease，It is a common disease that causes deafness and blindness, with a prevalence rate of 1/5000 to 1/16000 in the population. Usher syndrome is divided into three types: Usher syndrome type I, type II, and type III. USH type I exhibits near total deafness and vestibular dysfunction in childhood, and typically presents with RP symptoms before adulthood; Type II patients have moderate to severe hearing impairment, no vestibular dysfunction, and develop RP symptoms in adulthood; Type III patients are born with normal hearing, but gradually develop RP and hearing loss.
Introduction and inheritance mode of USH2A gene
The USH2A gene is located on chromosome 1q41 and encodes the Usherin protein. It has two splicing transcripts, long and short. One is Usherin protein subtype a encoded by 21 exons, with a total of 1546 amino acids, and the other is Usherin protein subtype b encoded by 51 exons found at the 3 terminus of the USH2A gene, with a total of 72 exons, encoding 5202 amino acids. This gene is mainly expressed in the cochlea and retina. USH2A gene mutations often cause Usher syndrome or non syndromic retinitis pigmentosa, inherited in an autosomal recessive manner.
USH2A gene mutation types
There are 124 variants of the FZD4 gene included in the HGMD database, most of which are point mutations or small fragment deletions/insertions, and a small number are large fragment insertions/deletions.
Disease phenotype caused by USH2A gene mutation
In addition to causing Usher syndrome, USH2A gene mutations can also cause diseases such as retinitis pigmentosa. The table shows the related diseases included in the HGMD database.
Case sharing
Clinical symptoms：The proband is a 32 year old female with a clinical diagnosis of Usher syndrome. The proband's relatives have no relevant symptoms and are sporadic cases.
Testing items：Genetic testing for ophthalmic genetic diseases (441 genes)
Test method ：Extract genomic DNA from the peripheral blood of the subject, construct a genomic library, capture relevant target gene exons and adjacent intron regions through probe hybridization, and enrich them. The enriched target gene fragments were sequenced using a high-throughput sequencing platform, and Sanger sequencing was used to validate the identified pathogenic variants.
Detection result ：Detect a pathogenic gene mutation that matches the clinical phenotype of the subject.
Note: According to the genetic variation classification criteria established by the American Society for Medical Genetics and Genomics (ACMG), mutations are divided into the following five types, with pathogenic mutations represented by pathogenic mutations; Likely pathogenic refers to a variant that may cause disease; Benign mutation; Like benign refers to a mutation that may be benign; Unknown significance refers to mutations with unclear meanings. AD stands for autosomal dominant inheritance; AR stands for autosomal recessive inheritance; X-linked represents X-linked inheritance.
Genetic analysis: (1) The USH2A (OMIM 608400) gene mutation often causes Usher syndrome or retinitis pigmentosa, which is inherited in an autosomal recessive manner.
(2) The tested proband carries the following heterozygous mutation: USH2A c.1000C>T; p. Arg334Trp， This mutation has been included in the HGMD database and has been reported as a pathogenic mutation in literature.
(3) USH2A c.1876C>T; p. Arg626*， This mutation has been included in the HGMD database and has been reported as a pathogenic mutation in literature.
Genetic counseling advice：(1) The tested father did not verify the site of this mutation. Suggest genetic counseling.
(2) When the test subject and other patients in the family give birth to children with a spouse carrying the USH2A gene mutation, 50% of the offspring will develop the disease, and 50% of the offspring will be carriers. The probability of male and female patients developing the disease is equal; When having children with a spouse who does not carry the USH2A gene mutation, the offspring are carriers. It is recommended to undergo genetic counseling during marriage and childbirth.
First generation verification results:
Reference:
1. Adato (2000) Hum Mutat 15, 388
2. Bravo-Gil (2016) Sci Rep 6: 23910 [Additional phenotype]
3. Weston (2000) Am J Hum Genet 66, 1199
4. Xiong (2015) Science 347: 1254806 [Additional report]
5. Fernández-Martínez (2011) Eur J Hum Genet 19, 445
CHIGENOVO Co., Ltd. is an ophthalmic gene therapy company, a national high-tech enterprise focusing on genetic diagnosis of genetic eye diseases and the development of gene therapy drugs. It is committed to providing "one-stop" services for patients with genetic eye diseases.
HUATAO GROUP
Contact Us
Telephone:400-6006223 010-82071936
Website:en.chinagene.cc
Address: Floor 4, Area D, Building 1, No.27 Life Garden Road, Zhongguancun Life Science Park, Changping District, Beijing
WeChat subscription account