OBJECTIVE: To explore the genetic basis of a patient with suspected Oculocutaneous albinism (OCA). METHODS: An OCA patient presented at the West China Second Hospital of Sichuan University and his mother were selected as the study subjects. Peripheral blood samples were collected for the extraction of, genomic DNA, and whole exome sequencing (WES) was carried out. Candidate variants were verified through specific primer amplification, Sanger sequencing, and agarose gel electrophoresis. Bioinformatic analysis and pathogenicity rating were conducted on the candidate variants. This study has been approved by the Medical Ethics Committee of West China Second Hospital (No. 2024-228). RESULTS: Genetic testing revealed that the patient had harbored variants in exon 1 of the TYR gene, including a c.157G>T (p.G53C) missense variant and a c.609dup (p.A204fs) frameshifting variant. Specific primer amplification and Sanger sequencing, combined with agarose gel electrophoresis, confirmed that these are compound heterozygous variants. Based on the guidelines from the ACMG, the c.157G>T was rated as likely pathogenic, and c.609dup was rated as pathogenic. Alphafold3 predicted that the variant proteins had significant structural changes. CONCLUSION The patient was diagnosed with OCA due to compound heterozygous variants of the TYR gene. Discovery of the c.609dup variant has enriched the mutational spectrum of OCA and provided a basis for genetic counseling and prenatal diagnosis for this patient.
Humans ; Albinism, Oculocutaneous/enzymology* ; Male ; Female ; Monophenol Monooxygenase/chemistry* ; Base Sequence ; Mutation, Missense

OBJECTIVETo detect potential mutations in genes related with non-syndromic oculocutaneous albinism I-IV and ocular albinism type I in two couples who had given births to children with albinism.

METHODSAll exons of the non-syndromic albinism related genes TYR, OCA2, TYRP-1, MITF, SLC45A2 and GPR143 were subjected to deep sequencing. The results were verified with Sanger sequencing.

RESULTSFor the two female carriers, the coding region of the TYR gene was found to harbor a frameshift mutation c.925_926insC, which was also suspected to have been pathogenic. In one of the male partners, a nonsense mutations c.832C>T was found, which was also known to be pathogenic. Another male partner was found to harbor a TYR gene mutation c.346C>T, which was also known to be a pathogenic nonsense mutation.

CONCLUSIONThe coding region of the TYR gene c.925_926insC (p.Thr309ThrfsX9) probably underlies the OCA1 disease phenotype.

Adult ; Albinism, Oculocutaneous ; enzymology ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Exons ; Female ; Frameshift Mutation ; Humans ; Male ; Membrane Glycoproteins ; genetics ; Molecular Sequence Data ; Mutation, Missense ; Oxidoreductases ; genetics ; Pedigree

OBJECTIVETo perform genotyping analysis and subsequent prenatal genetic diagnosis for two families affected with oculocutaneous albinism (OCA).

METHODSDirect sequencing of TYR and P genes was performed in two albino probands. Family members were screened for corresponding mutant alleles. Prenatal genetic diagnoses were performed at early pregnancy by chorionic villus sampling (CVS) at mid-pregnancy through amniocentesis.

RESULTSNo mutations were detected in the TYR gene in either probands, whereas 4 heterozygous mutations of the P gene were found, namely c.406C>T, c.535A>G, c.808-2A>G and c.2180T>C, among which c.535A>G and c.808-2A>G were novel. In the first round prenatal genetic testing, both fetuses were found to have the same genotypes as the probands. Both families had decided to terminate the pregnancy after genetic counseling. In the second round testing, neither of the fetuses was found to be affected by genotyping. The pregnancies continued and two healthy fetuses were born.

CONCLUSIONOCA can be classified by genotyping, with which reliable prenatal diagnosis and feasible genetic counseling may be provided.

Adolescent ; Adult ; Albinism, Oculocutaneous ; diagnosis ; embryology ; enzymology ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Child, Preschool ; Female ; Fetal Diseases ; diagnosis ; genetics ; Genotype ; Humans ; Infant ; Male ; Membrane Transport Proteins ; genetics ; Middle Aged ; Molecular Sequence Data ; Monophenol Monooxygenase ; genetics ; Pedigree ; Point Mutation ; Pregnancy ; Prenatal Diagnosis ; Young Adult

OBJECTIVETo evaluate the feasibility of genetic analysis of tyrosinase gene (TYR) in oculocutaneous albinism type I (OCA1). Mutation analysis and prenatal genetic diagnosis of TYR gene for seven pedigrees with OCA1 were performed.

METHODSPCR was used to amplify the exons, exon-intron boundaries and promoter of the TYR gene in the probands and/or their parents. The products were further analyzed by direct sequencing. Prenatal genetic diagnoses were performed by chorionic villus sampling after the genotypes of the probands or their parents were determined.

RESULTSCompound heterozygous mutations were detected in all pedigrees, which included 9 mutations, namely R76Q, c.232insGGG, R116X, R278X, R299H, c.929-930insC, IVS2-11delTT, Q399X and W400L. Among these, R76Q and Q399X were identified for the first time. Seven families have requested prenatal diagnoses. One fetus was detected with double mutations of TYR gene, and the parents have decided to have therapeutic abortion. Two fetuses did not carry the mutations identified in the probands, whilst other four fetuses were carriers of heterozygous mutations. Six families decided to carry on with the pregnancies. And the neonates did not show any symptoms of OCA after birth.

CONCLUSIONDirect sequencing of the TYR gene is helpful for genetic counseling, prenatal diagnosis and carriers screening of OCA1.

Albinism, Oculocutaneous ; diagnosis ; enzymology ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Infant, Newborn ; Male ; Monophenol Monooxygenase ; genetics ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; methods