OBJECTIVETo identify the mutations of the tyrosinase gene (TYR) and P gene in patients with oculocutaneous albinism (OCA).

METHODSPolymerase chain reaction (PCR) and denaturing high performance liquid chromatography (DHPLC) were applied to detect the mutations in all exons of TYR gene and P gene. Then DNA sequencing and restriction endonuclease analysis were used to confirm the mutations detected by DHPLC. Novel mutations were screened in 100 unrelated persons with normal phenotypes to exclude the possibility of polymorphism.

RESULTSTwo mutations were detected in the P gene of the three patients and none in TYR gene. Heterozygous mutation of T450M in exon 13 of the P gene was detected in patient 1. Patient 2 had a heterozygous mutation of T450M in exon 13 and a heterozygous mutation of G775R in exon 23 of the P gene. Patient 3 had a heterozygous mutation of G775R as well. Restriction endonuclease analysis of the P gene exon 13 showed that the Oli I site had partly disappeared resulting from the heterozygous mutation T450M in patient 1 and patient 2, but not in 100 unrelated individuals. The heterozygous mutation T450M is a novel mutation.

CONCLUSIONGene diagnosis of OCA can be carried out effectively by combining PCR, DHPLC, DNA sequencing and restriction endonuclease analysis.

Albinism, Oculocutaneous ; genetics ; Base Sequence ; Catechol Oxidase ; genetics ; Child, Preschool ; DNA Mutational Analysis ; Exons ; genetics ; Female ; Hermanski-Pudlak Syndrome ; genetics ; Humans ; Monophenol Monooxygenase ; genetics ; Mutation ; Young Adult

PURPOSE: To report optical coherence tomography (OCT) findings in albinism. METHODS: Full ocular examinations, including OCT, were performed in one patient with ocular albinism and two patients with oculocutaneous albinism. RESULTS: OCT scans were unable to detect the foveal depression in these patients. A widespread thickening of the retina occurred throughout the entire fovea, which showed no difference from the surrounding macula. OCT scans also demonstrated probable scleral layer below the retinal pigment epithelial (RPE) layer. CONCLUSIONS: OCT scans of albinism patients confirmed foveal hypoplasia and increased transmission of incident light in the RPE layer.
Albinism* ; Albinism, Ocular ; Albinism, Oculocutaneous ; Depression ; Humans ; Retina ; Retinaldehyde ; Tomography, Optical Coherence*

Oculocutaneous Albinism (OCA) is a heterogenous autosomal recessive disorder characterized by defective melanin biosynthesis. Physical findings including white scalp hair and depigmented skin of whole body in newborn infants are important clinical features of OCA 1. We report a newborn case of OCA 1 with two different TYR mutations, and gene defects of the baby revealed to be originated from both parents carriers of OCA.
Albinism, Oculocutaneous* ; Hair ; Humans ; Infant, Newborn* ; Melanins ; Parents ; Scalp ; Skin

Mycosis fungoides presenting with hypopigmented lesions is an uncommon variant, which is usually described among dark-skinned patients. We report a case of hypopigmented mycosis fungoides in an eight-year-old girl who has responded favorably to narrowband-ultraviolet B therapy. The disease mimics several benign inflammatory skin conditions, hence, a high clinical suspicion is warranted in patients presenting with widespread hypopigmentation.

Human ; Female ; Child ; Albinism, Oculocutaneous ; Hypopigmentation ; Mycosis Fungoides ; Skin ; Lymphoma

OBJECTIVE: To analyze gene variants in a Chinese pedigree with oculocutaneous albinism (OCA). METHODS: Gene sequencing of the proband and his parents was performed using chip capture high-throughput sequencing and Sanger sequencing techniques, and PolyPhen-2, SIFT, MutationTaster, and FATHMM software were used to predict the function of new variants. At the same time,the pedigree and variant genes of 4 albinism patients from this pedigree were analyzed. RESULTS: Sequencing results showed that the proband's TYR gene (NM_000372) has c.230G>A (p.Arg77Gln) and c.120_121insG (p.Asp42GlyfsTer35) compound heterozygous variants. The proband's father carries c.230G>A heterozygous variant, and the mother carries c.120_121insG heterozygous variant, indicating that the proband's two variants are from his father and mother. The former is a known missense variant, which can cause abnormal or loss of the original function of the protein polypeptide chain. The latter c.120_121insG(p.Asp42GlyfsTer35) is an unreported frameshift variant of the TYR gene subregion (EX1; CDS1). PolyPhen-2, SIFT, MutationTaster and FATHMM predictions are all prompted as "harmful variants". This variant caused the amino acid encoded protein to terminate prematurely, producing a truncated protein, which eventually formed a 76-amino acid short-type TYR protein instead of the 529-amino acid wild-type TYR protein. Through the pedigree analysis, the four patients in the pedigree are all of the same type of compound heterozygous variants, and the disease-causing genes are all from the patient's parents. They belong to a special form of consanguineous marriage within 5 generations. CONCLUSION The compound heterozygous variants of c.230G>A (p.Arg77Gln) and c.120_121insG (p.Asp42GlyfsTer35) of the TYR gene may underlie the disease in this pedigree. The gene sequencing results enrich the variant spectrum of the TYR gene, and has facilitated molecular diagnosis for the patient.
Albinism, Oculocutaneous/genetics* ; Consanguinity ; Heterozygote ; Humans ; Mutation ; Pedigree

OBJECTIVE: To assess the value of non-invasive prenatal testing based on cfDNA barcode-enabled single-molecule test (cfBEST) for the prenatal diagnosis of oculocutaneous albinism type I in a family. METHODS: Prenatal genetic diagnosis was carried out by using the cfBEST-based method as well as invasive prenatal diagnosis through amniocentesis. The outcome of the pregnancy was followed up. RESULTS: Non-invasive prenatal testing based on cfBEST showed a fetal DNA concentration of 6.6%, with the proportion of c.929_930insC (p.Arg311Lysfs*7) and c.1037-7T>A mutations being 45.7% and 0%, respectively. The posterior frequency of the negative results was 1, suggesting that the fetus carried neither of the two mutations. The result was consistent with that of invasive prenatal diagnosis, and the follow-up found that the fetus was normal. CONCLUSION Non-invasive prenatal testing based on cfBEST can be used to detect maternal and fetal genotypes in maternal cell-free DNA, which is clinically feasible.
Albinism ; Albinism, Oculocutaneous/genetics* ; Amniocentesis ; Cell-Free Nucleic Acids ; Female ; Humans ; Pregnancy ; Prenatal Diagnosis

Albinism is a hereditary disease caused by the defect of tyrosinase that converts tyrosine to dihydroxyphenylalanine (DOPA). `Oculocutaneous albinism' is classified as hypopigmentation of skin, hair and eyes, but incidences of `ocular albinism' where hypopigmentation is limited to eyes are found rarely. Biochemically, albinism is caused by the tyrosinase activity. Typical findings in oculocutaneous albinism include not only ophthalmologic problems such as hypopigmentation of skin, foveal hypoplasia, photophobia and decreased visual acuity but also congenital nystagmus. We cannot determine distinctive characteristics of nystagmus of albinism because domestically, there are only a few reports that have been recorded correctly about nystagmus of albinism. Merely, we present our experience of two cases of albinism with congenital nystagmus because we think that these two cases, showing different types of nystagmus and electronystagmography, stand for the two representative types of nystagmus found in the literature up to date.
Albinism ; Albinism, Oculocutaneous* ; Dihydroxyphenylalanine ; Electronystagmography ; Genetic Diseases, Inborn ; Hair ; Hypopigmentation ; Incidence ; Monophenol Monooxygenase ; Nystagmus, Congenital* ; Photophobia ; Skin ; Tyrosine ; Visual Acuity

Oculocutaneous albinism (OCA) is a group of inherited disorders of the melanin synthesizing system, and these are characterized by hypopigmentation of the hair, skin and eyes, with a normal number of melanocytes. The defect of melanin biosynthesis is caused by genetic mutation of such enzymes as tyrosinase (TYR), and tyrosinase-related protein (TYRP), which affect tyrosine convert to melanin pigment. There are at least four types of OCA from OCA1 to OCA4. The different types of OCA are caused by mutations in different genes. The most severe form, OCA1A, is distinguishable from other forms owing to a complete lack of melanin pigment throughout the patient's whole life. But among other types, except OCA1A, it is hard to identify the correct type according to only the clinical findings because their clinical phenotypes usually overlap. Therefore, molecular study is a useful tool for the typing and diagnosis of OCA. We experienced a case of a 10-month-old male toddler who has pale skin, straw-colored hair, nystagmus and visible choroidal vessels. Under the clinical impression of OCA, the correct subtyping was made on the basis of genetic analysis of the chromosomes and we found a new TYR gene frame-shift mutation.
Albinism, Oculocutaneous ; Choroid ; Eye ; Hair ; Humans ; Hypopigmentation ; Infant ; Male ; Melanins ; Melanocytes ; Monophenol Monooxygenase ; Phenotype ; Skin ; Tyrosine

A 4-month-old female maltese dog was admitted to Veterinary Medical Teaching Hospital of Seoul National University for evaluation of abnormal color of bilateral irises. This patient had the photophobia in the light and exhibited the complete absence of pigment resulting in white hair, pink muzzle, eyelids and foot-pads. Central zone of the irises were yellow in color influenced by tapetal reflex, and peripheral zone were pale blue. The iridal capillaries were transparented on the irises. Ophthalmoscopic examination revealed a yellow tapetal fundus but no pigment in the nontapetal fundus.
Albinism, Oculocutaneous/diagnosis/*veterinary ; Animals ; Dog Diseases/*diagnosis ; Dogs ; Female ; Ophthalmoscopy/veterinary ; Photophobia/diagnosis/veterinary

OBJECTIVETo provide prenatal diagnosis for two families affected with oculocutaneous albinism (OCA), in both of which only 1 pathogenic allele has been identified.

METHODSTo determine the clinical classification of OCA through DNA sequencing for TYR, P, TYRP1 and SLC45A2 genes in combination with phenotype analysis. Prenatal diagnosis was carried out by direct sequencing and intragenic SNPs family-based linkage analysis.

RESULTSIn the first family, only 1 heterozygous mutation c.1255C>T was found in the proband, which was inherited from her mother. Together with its clinical phenotype, the proband was suspected to have OCA2 Screening of amniotic fluid, however, has found no mutation. With family-based linkage analysis, the fetus was deemed to be an OCA2 carrier. In the second family, again only one heterozygous mutation c.1920_1949 del30bp and ins AACA was found in the proband, which was inherited from her father. Together with its clinical phenotype, the proband was suspected to have OCA2. Screening of amniotic fluid has revealed a heterozygous mutation c.1920_1949 del30bp and ins AACA. By family-based linkage analysis, the fetus was deemed to be an OCA2 carrier. Both fetuses had a normal phenotype at birth.

CONCLUSIONPrenatal genetic diagnosis has been provided for the first time for two families affected with OCA, in which only 1 pathogenic mutant allele was detected. The combined mutation detection and SNPs linkage analysis has turned out to be successful.

Albinism, Oculocutaneous ; genetics ; Female ; Genetic Linkage ; Humans ; Male ; Mutation ; Polymorphism, Single Nucleotide ; Prenatal Diagnosis