Biomedical subjects

Atsushi Kanai

Publications and source records attributed to Atsushi Kanai.

At least 19 recordsLinked to original sources

PubMed2005

[Analysis of gene mutation in Chinese patients with Reis-Bücklers corneal dystrophy].

OBJECTIVE: To identify the mutation of the TGFBI gene in Chinese patients with Reis-Bücklers corneal dystrophy, and to study the relationship between the gene mutation and the clinical appearance. METHODS: Ten patients and 2 unaffected family members from 2 unrelated families with corneal dystrophy were studied. Molecular genetic analysis was performed on DNA extracted from peripheral leucocytes, and exons 4 and 12 of the TGFBI gene were amplified by polymerase chain reaction for direct sequencing. RESULTS: Both pedigrees showed an autosomal dominant inheritance. The clinical appearance of the cornea consisted of fine granular, subepithelial opacities which spread and become confluent with time, and resembled geographic type of Reis-Bücklers corneal dystrophy. Direct sequencing of all affected members revealed a G-to-T transition at codon 124 (CGC to CTC), producing R124L mutation of TGFBI gene. CONCLUSIONS: R124L mutation of the TGFBI gene is found in two Chinese families with Reis-Bücklers corneal dystrophy. The phenotype of Reis-Bücklers corneal dystrophy in both families belongs to the geographic type. Molecular genetic approach may be useful for the proper diagnosis of this type of corneal dystrophy.

Adolescent↗

PubMed2004

Truncation and mutagenesis analysis of the human X-arrestin gene promoter.

X-arrestin (arrestin-3) is an arrestin present specifically in the outer segments of red-, green-, and blue-cone photoreceptors. The X-arrestin gene is on Xcen-q22, and consists of 17 exons with a promoter containing a TATA box and elements important for photoreceptor expression, including three CRX and one PCE-1-like element. In order to delineate the promoter structure necessary for the pan-cone-specific expression of X-arrestin, the expression of the gene in retinoblastoma cell lines was investigated, and a structure-function analysis of the promoter was conducted in the appropriate cellular substrate. Expression of X-arrestin was detected at a low level in the Y79 retinoblastoma cell line but not in the WERI retinoblastoma cell line. Truncation and expression analysis of the X-arrestin promoter in Y79 showed maximal activity in the proximal 378-bp region containing the CRX and PCE-1-like elements upstream of the TATA and CAAT boxes and a negative regulator in the distal 1-2-kbp region. Mutagenesis of the three CRX and PCE-1-like elements and expression analysis demonstrated complete elimination of the promoter activity. Mutagenesis of the TATA box and PCE-1-like element individually resulted in similar decrease in promoter activity, but the decrease in the promoter activity was greater when the CRX elements were mutagenized with a 5' to 3' spatial gradient in the negative effect, suggesting a cooperative effect of the three CRX elements. The regulation of expression from this promoter may involve the binding of a multi-protein enhanceosome complex at the CRX triplet and the PCE-1-like element, resulting in the recruitment and activation of the RNA polymerase II complex at the downstream TATA box.

Arrestins↗

PubMed2004

Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2.

Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive retinal dystrophy characterized by multiple glistening intraretinal crystals scattered over the fundus, a characteristic degeneration of the retina, and sclerosis of the choroidal vessels, ultimately resulting in progressive night blindness and constriction of the visual field. The BCD region of chromosome 4q35.1 was refined to an interval flanked centromerically by D4S2924 by linkage and haplotype analysis; mutations were found in the novel CYP450 family member CYP4V2 in 23 of 25 unrelated patients with BCD tested. The CYP4V2 gene, transcribed from 11 exons spanning 19 kb, is expressed widely. Homology to other CYP450 proteins suggests that CYP4V2 may have a role in fatty acid and steroid metabolism, consistent with biochemical studies of patients with BCD.

Chromosomes, Human, Pair 4↗

PubMed2004

Compound heterozygous mutations of M1S1 gene in gelatinous droplike corneal dystrophy.

PURPOSE: To report the genetic findings in a Chinese patient diagnosed with gelatinous droplike corneal dystrophy (GDLD). DESIGN: Case report and experimental study. METHODS: Molecular genetic analysis was performed on the DNA extracted from peripheral leukocytes from a Chinese patient with GDLD and his unaffected parents. Fifty healthy, unrelated, Chinese participants were used as control subjects. The M1S1 gene was amplified by polymerase chain reaction and directly sequenced. RESULTS: The patient was clinically diagnosed with GDLD. Direct sequencing of the M1S1 gene revealed heterozygous changes in both alleles, a novel Y184C mutation on one allele and a Q118X mutation on the other that was reported as a founder mutation in the Japanese population. The patient's unaffected parents showed only the heterozygous Q118X or Y184C mutation. The mutation was not detected in the 50 unaffected subjects. CONCLUSIONS: This is the first genetic analysis of a Chinese patient with GDLD. Because the compound heterozygote mutations Q118X and Y184C cosegregated with the phenotype, they are likely the cause of GDLD in this patient.

Adolescent↗

PubMed2004

Microarray analysis identified differentially expressed genes in keratocytes from keratoconus patients.

PURPOSE: To identify differentially expressed genes in human keratoconus keratocyte by cDNA microarray. METHODS: Normal and keratoconic cornea were cultured for keratocytes. RNA was extracted. cDNA probe labeled with fluorescence dye was made from Poly A+ RNA, hybridized with microarray slide, containing 164 human apoptosis genes. Signal intensity was measured. Expression ratio between keratoconus and normal was determined using ImaGene Ver.3.0. Identified genes were further evaluated by RT-PCR and real-time PCR. RESULTS: Five over-expressed and four under-expressed genes were identified. Of these, differential expression of tumor necrosis factor alpha-induced protein 6 (TNFAIP6), human insulin-like growth factor binding protein 5 (IGFBP5), and IGFBP3 were verified and confirmed by RT-PCR. Real-time PCR showed TNFAIP6 increased by 3.3 folds, while IGFBP5, IGFBP3 decreased by 14 and 11 folds respectively. CONCLUSIONS: The identified genes could be important and deserve further investigation. Significant differential expression of TNFAIP6, IGFBP5, and IGFBP3 may indicate an important role of these genes in the mechanism underlying stromal thinning.

Adult↗

PubMed2004

[Case of late onset and isolated lattice corneal dystrophy with Asn544Ser (N544S) mutation of transforming growth factor beta-induced (TGFBI, BIGH3) gene].

PURPOSE: To report a case of lattice corneal dystrophy (LCD) with Asn544Ser (N544S) mutation of the transforming growth factor beta-induced (TGFBI) gene. CASE: A 68-year-old male patient with late-onset, sporadic LCD without corneal erosion. Amyloid deposits showing dot and lattice lines were seen in the mid to deep stroma. After obtaining appropriate informed consent, genomic DNA was amplified by polymerase chain reaction (PCR) and directly sequenced. RESULTS: A heterozygous single base pair transition (AAT --> AGT), resulting in substitution of serine for asparagine at codon 544 of the TGFBI gene, was detected. CONCLUSION: The case was classified as atypical type IV because of the late onset, lack of corneal erosion, and amyloid deposits in the mid to deep stroma.

Aged↗

PubMed2003

A novel mutation of M1S1 gene found in a Vietnamese patient with gelatinous droplike corneal dystrophy.

To identify the genetic defect in the M1S1 gene responsible for gelatinous droplike corneal dystrophy (GDLD) in a Vietnamese family.Experimental study. Blood samples were collected from a patient and the unaffected members of a GDLD-affected family. Fifty normal unrelated subjects of Vietnamese origin were used as controls. Genomic DNA was extracted from blood leukocytes. DNA analysis of the M1S1 gene was performed using polymerase chain reaction and direct sequencing. Sequencing of the M1S1 gene revealed a deletion of a 12-base-pair (bp) fragment from nucleotide positions 772 to 783 [772 to 783del(ATCTATTACCTG)], resulting in a loss of four amino acids at codons 258 to 261 (L258-liter261del). Yet, an insertion of nucleotide T in place of the missing sequence (772insT) was found. This combined mutation was homozygous in the GDLD-affected patient and heterozygous in his unaffected son and younger sister. Such genetic alteration was excluded in the control population. This is the first report of a mutational analysis performed in a Vietnamese patient with GDLD. In this family, the novel 772 to 783del(ATCTATTACCTG) + 772insT mutation on the M1S1 gene was well cosegregated with the phenotype and thus expected to cause GDLD. Although the M1S1 gene was responsible for GDLD in Vietnamese patients, the mutation found here is completely different from that previously reported in Japanese patients, where GDLD is most frequently seen.

Adult↗

PubMed2003

Long-term follow-up for bullous keratopathy after sato-type anterior-posterior corneal refractive surgery.

PURPOSE: To evaluate cases of bullous keratopathy resulting from anterior-posterior radial corneal keratotomy (Sato-type operation) performed from 1951 to 1959. DESIGN: Observational case series. METHODS: Records for a total of 220 eyes of 139 patients with follow-up examinations were examined. The age at operation vs time to occurrence of bullous keratopathy after the original operation was evaluated in four age groups. Endothelial cell density was measured in 11 long-term postoperative eyes. RESULTS: The mean time to development of bullous keratopathy after surgery was 26.9 +/- 8.8 years (mean +/- SD; n = 173 eyes). The length of this period was not affected by the age of the patient at the time of the original surgery. Average endothelial cell density in 11 eyes of 11 patients 28.5 +/- 3.7 years after surgery was 639 +/- 135 cells/mm(2). CONCLUSIONS: Although some corneas remained clear more than 26 years after anterior-posterior radial keratotomy, the risk of late corneal decompensation continues to exist for these patients.

Cell Count↗

PubMed2003

Smad7 suppresses the inhibitory effect of TGF-beta2 on corneal endothelial cell proliferation and accelerates corneal endothelial wound closure in vitro.

PURPOSE: The inhibitory activity of transforming growth factor-beta2 (TGF-beta2) on corneal endothelial cell proliferation is thought to be a cause of the limited regenerative capacity of corneal endothelial cells that may be related to impaired corneal transparency when many corneal endothelial cells are lost due to various stresses. We determined whether Smad7, an intracellular antagonist of TGF-beta signaling, regulated the inhibitory activity of TGF-beta2 or aqueous humor on corneal endothelial cell proliferation. METHODS: The effect of Smad7 on TGF-beta2- or aqueous humor-mediated inhibition of corneal endothelial cell proliferation was evaluated using thymidine uptake assay with cultured rabbit corneal endothelial cells infected with adenovirus carrying Smad7. Expression of Smad or cell cycle-related proteins was detected by immunoblotting. In addition, a small scrape wound was made across a monolayer of Smad7-expressing cultured rabbit corneal endothelial cells to examine the effect of Smad7 on the wound-healing process in vitro. RESULTS: Overexpression of Smad7 abolished the inhibitory effect of TGF-beta2 or aqueous humor on the proliferation of cultured rabbit corneal endothelial cells associated with the inhibition of phosphorylation of Smad2 and downregulation of p27kip1. Smad7-overexpressing cultured rabbit corneal endothelial cells exhibited shorter wound closure time in the presence of aqueous humor than LacZ-expressing cells. CONCLUSION: Overexpression of Smad7 suppressed the inhibitory effect of TGF-beta2 or aqueous humor on corneal endothelial cell proliferation and accelerated corneal endothelial wound closure in vitro. Modification of Smad7 expression in corneal endothelial cells may thus have applicability in the treatment of wounded corneal endothelium.

Adenoviridae↗

PubMed2003

Identification of novel mutations of the CHST6 gene in Vietnamese families affected with macular corneal dystrophy in two generations.

PURPOSE: To report the clinical and genetic findings of Vietnamese families affected with macular corneal dystrophy (MCD) in 2 generations. METHODS: Two families, including 7 patients and 3 unaffected members, were examined clinically. Blood samples were collected. Fifty normal Vietnamese individuals were used as controls. Genomic DNA was extracted from leukocytes. Analysis of the carbohydrate sulfotransferase (CHST6) gene was performed using polymerase chain reaction and direct sequencing. RESULTS: The typical form of MCD was recognized in family B, in which sequencing of CHST6 gene revealed an nt 1067-1068ins(GGCCGTG) mutation (frameshift after 125V) homozygously in MCD patients and heterozygously in the unaffected members. Family N also showed clinical features of MCD, moderate in the mother but severe in the affected son. Sequencing revealed a single heterozygous Arg211Gln in the mother, compound heterozygous Arg211Gln+ Gln82Stop in the affected son, and heterozygous Arg211Gln mutation in the unaffected members. The identified mutations in these pedigrees were excluded from normal controls. CONCLUSIONS: The novel frameshift and compound heterozygous mutations might be responsible for MCD in the families studied. The phenotypic variation between affected parents and offspring was unclear. In family N, severe MCD phenotype seen in the affected son may be due the fact that he had an early stop codon mutation (Gln82Stop).

Adolescent↗

PubMed2003

Mutations in the CHST6 gene in patients with macular corneal dystrophy: immunohistochemical evidence of heterogeneity.

PURPOSE: Macular corneal dystrophy (MCD) is an autosomal recessive disorder leading to severe visual impairment. The carbohydrate sulfotransferase 6 (CHST6) gene, which encodes the corneal N-acetylglucosamine 6-O-sulfotransferase on 16q22 has been identified as a causative gene for MCD. The purpose of this study was to identify mutations in CHST6 in Japanese patients with MCD and evaluate them by means of immunohistochemistry. METHODS: CHST6 was screened in 7 patients and 45 healthy control subjects. Genomic DNA was isolated, and the open reading frame (ORF) of CHST6 was amplified by polymerase chain reaction (PCR). PCR products were analyzed by direct sequencing and restriction enzyme digestion. Immunohistochemistry with a monoclonal anti-keratan sulfate (KS) antibody was performed on corneas of four patients from three families. RESULTS: Three novel mutations (P204Q, R205L, and R177H) and two previously reported mutations (R211W and A217T) were identified in the ORF of CHST6. P204Q, R205L, and R211W were found to be homozygous and R177H and A217T compound heterozygous with R211W on another allele. Immunohistochemistry revealed that R205L homozygous cornea had negative reactivity against the anti-KS antibody, representing type I MCD, and that R211W homozygous and R211W/A217T compound heterozygous corneas had negative or very weak reactivity in the stroma with antibody positive deposits, which were distinct from any previously reported types. CONCLUSIONS: Two mutations (homozygoous R211W and compound heterozygous R211W/A217T) should be subclassified immunohistochemically into new phenotypes of MCD. This heterogeneity could provide further insights into the pathogenesis of MCD.

Amino Acid Sequence↗

PubMed2003

Mutation analysis of the carbohydrate sulfotransferase gene in Vietnamese with macular corneal dystrophy.

PURPOSE: Mutations in a new carbohydrate sulfotransferase gene (CHST6) encoding corneal N-acetylglucosamine-6-sulfotransferase (C-GlcNac-6-ST) have been identified as the cause of macular corneal dystrophy (MCD) in various ethnicities. This study was conducted to examine the CHST6 gene in Vietnamese with MCD. METHODS: Nineteen unrelated families, including 35 patients and 38 unaffected relatives were examined clinically. Blood samples were collected. Fifty normal Vietnamese individuals served as control subjects. Genomic DNA was extracted from leukocytes. Analysis of the CHST6 gene was performed with polymerase chain reaction and direct sequencing. Corneal buttons were studied histopathologically. RESULTS: A slit lamp examination revealed clinical features of MCD with gray-white opacities and stromal haze between. On histopathology, corneal sections showed positive staining with colloidal iron. Sequencing of the CHST6 gene revealed six homozygous and three compound heterozygous mutations. The homozygous mutations, including L59P, V66L, R211Q, W232X, Y268C, and 1067-1068ins(GGCCGTG) were detected, respectively, in two, one, eight, one, one, and two families. Compound heterozygous mutations R211Q/Q82X, S51L/Y268C, and Y268C/1067-1068ins(GGCCGTG) were identified, each in one family. A single heterozygous change at codon 76 (GTG-->ATG) was detected in family L, resulting in a valine-to-methionine substitution (V76M). None of these mutations was detected in the control group. CONCLUSIONS: Mutations identified in the CHST6 gene cosegregated with the disease phenotype in all but one family studied and thus caused MCD. Among these, the R211Q detected in 9 of 19 families may be the most common mutation in Vietnamese. These data also indicate that significant allelic heterogeneity exists for MCD.

Adolescent↗

PubMed2003

Molecular cloning of ELOVL4 gene from cynomolgus monkey (Macaca fascicularis).

ELOVL4, elongation factor of very long chain fatty acids-4, is known to be responsible for autosomal dominant macular degeneration and Stargardt-like macular degeneration. In this study, we cloned the monkey homologue of ELOVL4 and determined the cellular and tissue distribution of the gene product. Sequence analysis of the monkey ELOVL4 gene revealed a high degree of homology between human and monkey. The cloned full-length cDNA of monkey ELOVL4 encoded 314 amino acids, the same length as human and two amino acids longer than mouse. The monkey ELOVL4 conserved the characteristics typical of the super family of ELO enzymes involved in the metabolism of membrane-bound fatty acid elongation. Real-time quantitative PCR demonstrated that the monkey ELOVL4 gene was highly expressed in restricted tissue-specific fashion, not only in the retina but also in the skin (90% of retina) and thymus (111% of retina). Immunohistochemical analysis detected signals predominantly in the photoreceptor layer of the monkey retina.

Amino Acid Sequence↗

PubMed2003

[Gene transfer into corneal endothelial cells by Helios gene gun].

PURPOSE: To examine the efficiency of particle-mediated gene transfer into rabbit corneal endothelium with a Helios gene gun system. METHODS: Using gene gun, plasmid DNA coding for green fluorescent protein(GFP) was transferred into cultured rabbit endothelial cells and rabbit corneal grafts from their endothelial site. Then the transferred corneas were transplanted as autografts. The GFP expression was detected by fluorescence microscopy. Histological examination of corneas was performed by light microscope and scanning electron microscope. RESULTS: In cultured rabbit endothelial cells, the transfection efficiency without damage to cells was about 7% under optimized helium pressure of 120 psi. In ex vivo, the GFP expression was limited to endothelial cells of the grafts at 140 psi. The histological findings from light and scanning electron microscopy of the grafts showed no severe mechanical damage in endothelial cells penetrated by gold particles. CONCLUSIONS: The helios gene gun system successfully transferred genes into corneal endothelial cells. However, further studies will be required to obtain the stable results of the particle mediated gene transfer into the endothelial cells of corneal grafts for clinical practice.

Animals↗

PubMed2002

Localization of Fas ligand in cytoplasmic granules of CD8+ cytotoxic T lymphocytes and natural killer cells: participation of Fas ligand in granule exocytosis model of cytotoxicity.

Fas ligand (FasL) has been implicated in cytotoxic T lymphocyte (CTL)- and natural killer (NK) cell-mediated cytotoxicity. In the present study, we investigated the localization of FasL in murine CTL and NK cells. Immunocytochemical staining showed that FasL was stored in cytoplasmic granules of CD8+ CTL clones and in vivo activated CTL and NK cells, where perforin and granzyme A also resided. Immunoelectron microscopy revealed that FasL was localized on outer membrane of the cytoplasmic granules, while perforin was localized in internal vesicles. Western blot analysis showed that the membrane-type FasL of 40 kDa was stored in CD8+ CTL clones but not in CD4+ CTL clones. By utilizing a granule exocytosis inhibitor (TN16), we demonstrated that FasL translocated onto cell surface upon degranulation of anti-CD3-stimulated CD8+ CTL clones. Moreover, TN16 markedly inhibited the FasL-mediated cytotoxicity by CD8+ T cell clones and NK cells. These results suggested a substantial contribution of FasL to granule exocytosis-mediated target cell lysis by CD8+ CTL and NK cells.

Animals↗

PubMed2002

Transthyretin Ser-44 mutation in a case with vitreous amyloidosis.

PURPOSE: To report a case of vitreous amyloidosis associated with a transthyretin Ser-44 mutation. METHODS: Interventional case report. A 44-year-old Japanese woman had a 2-month history of visual disturbance in both eyes. The vitreous and conjunctival specimens were subjected to histopathological examination. DNA was isolated from peripheral blood cells of the patient. The transthyretin gene was amplified and directly sequenced. RESULTS: The vitreous and conjunctiva specimens showed typical light microscopic features of amyloidosis. Direct sequencing of the transthyretin gene revealed a single base-pair substitution, which results in an amino acid substitution at position 44, phenylalanine to serine (transthyretin Ser-44). CONCLUSION: Transthyretin Ser-44 may cause vitreous amyloidosis.

Adult↗

PubMed2002

[The pathogenesis and treatment of corneal disorders].

In this 21 st century, it is predicted that blindness caused by corneal disorders which are difficult to prevent or treat will increase. It is important to study the pathogenesis, prevention, and treatment of these corneal disorders. Two corneal disorders, keratoconus and corneal dystrophy, were investigated to elucidate the pathogenesis by using molecular biological or molecular genetic techniques. Corneal transplantation is performed to restore vision of patients with corneal disorders, but the condition of the donor corneal endothelium is the key to maintaining transparency of the grafted cornea. We investigated the function or cell cycle mechanism of corneal endothelium at the level of the gene, and we also studied induced genes of endothelial cells during preservation of donor corneas. 1. Keratoconus: We searched for keratoconus patients with questionnaires sent to 141 hospitals in the 23 Wards of Tokyo. The incidence of patients was estimated to be 12.4 x 10(-5) for males and 6.7 x 10(-5) for females. The male/female ratio was 1.7: 1.0. The number of male patients was low when compared with studies reported 17 years ago. Rupture of Descemet's membrane in males was significantly higher than in females. Genesis of incidence: Apoptosis-related gene expression in thinning of the cornea was analyzed with cDNA microarrays, using mRNA isolated from cultured keratocytes of normal human corneas and keratoconus corneas. The expression of tumor necrosis factor alpha-induced protein 6(TNFAIP 6) was more enhanced, while insulin growth factor binding protein 5(IGFBP 5) was less expressed in keratoconus patients. 2. Corneal dystrophy: In corneal dystrophy related to four candidate genes such as transforming growth factor beta-induced(TGFBI) gene, membrane component 1 surface maker 1(M 1 S 1) gene, carbohydrate sulfotransferase gene 6(CHST 6), and collagen type VIII alpha-2(COL8 A 2) gene, 208 Japanese and 42 Vietnamese families were analyzed for the gene mutation and studied for the frequency of gene mutation and differences of clinical features. About 80% of Japanese with corneal dystrophies had mutation of the TGFBI gene and about 70% of them had Avellino corneal dystrophy. However, in Vietnamese patients, mutations were found in both the TGFBI gene (lattice corneal dystrophy; the phenotype gene was His 626 Arg) and in the CHST gene. The difference in frequency in gene mutations was significant between the two nationalities. Moreover, a novel corneal dystrophy associated with Asp 123 His mutation in TGFBI gene was found in one Vietnamese family. 3. Corneal endothelial cell: 1) gene expression: We performed random sequence and homology research analysis of 1,000 clones from a rabbit corneal endothelial cDNA library. Forty-five genes, including collagen type VIII alpha-1, were listed for the frequently observed cDNA in the library. 2) gene transfection: One of the causes of a growth-arrested state in human corneal endothelium was thought to be the presence of transforming growth factor-beta (TGF-beta) in aqueous humor. The transfection of Smad 7 gene, which blocks the signal, showed proliferation of the endothelial cells in the presence of aqueous humor. This suggests that there may be a possible practical application for using gene transfection with a non-viral DNA vector or with an adenovirus vector.

Adolescent↗

PubMedDate not supplied

Mutation analysis of the TGFBI gene in Vietnamese with granular and Avellino corneal dystrophy.

PURPOSE: Mutations of the human transforming growth factor beta-induced gene (TGFBI) were reported to cause granular (GCD) and Avellino (ACD) corneal dystrophy in various nationalities. In this study we examined the TGFBI gene in a Vietnamese population with GCD and ACD. METHODS: Eight unrelated Vietnamese families, including 20 affected and 24 unaffected individuals, were examined; 50 normal Vietnamese individuals were used as controls. Genomic DNA was extracted from peripheral blood leukocytes. The TGFBI gene was analyzed using the polymerase chain reaction and direct sequencing. The corneal button was studied. RESULTS: Slit-lamp examination revealed typical features of GCD in most cases. A few features of ACD and a patient with an atypical form of GCD were also seen. Histopathological analysis of a GCD cornea showed deposits that stained bright red with Masson trichrome. Sequencing revealed three distinct mutations: R555W in six families, R124H in one family, and D123H in another. CONCLUSIONS: R555W and R124H mutations were co-segregated with the disease phenotype and thus caused GCD and ACD, respectively, in the families studied. The R555W detected in six of the eight families indicates that the GCD phenotype may be the most common in Vietnamese individuals, unlike in other Asians (Japanese and Korean), where ACD is most common (>90%). The D123H mutation may cause an atypical variant of GCD.

Adolescent↗