Yu-Yuan Ke

A recurrent ITGA9 missense mutation in human fetuses with severe chylothorax: possible correlation with poor response to fetal therapy

To assess the possible correlations between the reported candidate genes (VEGFR3, FOXC2, ITGA9 and ITGB1) and the clinical response in fetuses with severe congenital chylothorax (CC) treated by prenatal OK‐432 pleurodesis.

Complex Rearrangements Between Chromosomes 6, 10, and 11 With Multiple Deletions at Breakpoints

Here we report on a girl with minor facial anomalies, cleft palate, seizures, microcephaly, psychomotor retardation, and a congenital heart defect. Complex of cytogenetic methods [GTG‐banding, spectral karyotyping (SKY), fluorescence in situ hybridization (FISH), multicolor banding (mBAND), and comparative genomic hybridization (array CGH)] showed complex chromosomal rearrangements (CCRs) involving chromosomes 6, 10, and 11 and 4 deletions at the breakpoints. Her father had an unrelated translocation between chromosomes 3 and 16, suggesting the possibility of an autosomal dominant trait that predisposes to complex synapses and recombination between multiple chromosomes during meiosis. This study demonstrates the power of combining available chromosome analysis technologies in resolving CCR.

A case of restrictive dermopathy with complete chorioamniotic membrane separation caused by a novel homozygous nonsense mutation in the ZMPSTE24 gene.

A Case of Restrictive Dermopathy With Complete Chorioamniotic Membrane Separation Caused by a Novel Homozygous Nonsense Mutation in the ZMPSTE24 Gene Ming Chen, Hsiang-Hsu Kuo, Yi-Chen Huang, Yu-Yuan Ke, Shun-Ping Chang, Chih-Ping Chen, Dong-Jay Lee, Meng-Luen Lee, Mei-Hui Lee, Tze-Ho Chen, Chia-Hsiang Chen, Hui-Mei Lin, Chin-San Liu, and Gwo-Chin Ma* Department of Genomic Medicine, Changhua Christian Hospital, Changhua, Taiwan Department of Medical Research, Changhua Christian Hospital, Changhua, Taiwan Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan Department of Obstetrics and Gynecology, Puli Christian Hospital, Nantou, Taiwan Department of Pediatrics, Puli Christian Hospital, Nantou, Taiwan Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan Department of Neurology, Vascular Biology and Genomics Center, Changhua Christian Hospital, Changhua, Taiwan Institute of Biochemistry and Biotechnology, Chung-Shan Medical University, Taichung, Taiwan

A compound heterozygous GNPTAB mutation causes mucolipidosis II with marked hair color change in a Han Chinese baby

A Compound Heterozygous GNPTAB Mutation Causes Mucolipidosis II With Marked Hair Color Change in a Han Chinese Baby Gwo-Chin Ma, Yu-Yuan Ke, Shun-Ping Chang, Dong-Jay Lee, and Ming Chen* Department of Genomic Medicine, Changhua Christian Hospital, Changhua, Taiwan Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan Department of Obstetrics and Gynecology, National Taiwan University, Taipei, Taiwan Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan Department of Life Sciences, Tunghai University, Taichung, Taiwan

Two Frequent Mutations Associated with the Classic Form of Propionic Acidemia in Taiwan

Propionyl-CoA carboxylase (PCC) is involved in the catabolism of branched chain amino acids, odd-numbered fatty acids, cholesterol, and other metabolites. PCC consists of two subunits, α and β, encoded by the PCCA and PCCB genes, respectively. Mutations in the PCCA or PCCB subunit gene may lead to propionic acidemia. In this study, we performed mutation analysis on ten propionic acidemia patients from eight unrelated and nonconsanguineous families in Taiwan. Two PCCA mutations, c.229C→T (p.R77W) and c.1262A→C (p.Q421P), were identified in a PCCA-deficient patient. Six mutations in the PCCB gene, including c.-4156_183+3713del, c.580T→C (p.S194P), c.838dup (p.L280Pfs*11), c.1301C→T (p.A434V), c.1316A→G (P.Y439C), and c.1534C→T (p.R512C), were identified in seven PCCB-deficient families. The c.-4156_183+3713del mutation is the first known large deletion that affects the PCCB gene functions. Furthermore, the c.1301C→T and c.-4156_183+3713del mutations in the PCCB gene have not been reported previously. Clinical features demonstrated that these two frequent mutations are associated with low enzyme activity and a classic propionic acidemia phenotype.

Prenatal transient alveolomaxillary defect in a case of mucolipidosis II (I‐cell disease)

Mucolipidosis II (ML II or I-cell disease) is a rare inherited lysosomal storage disease that causes multisystem deterioration and death in early childhood. Little is known about the fetal features of this condition, and therefore the diagnosis is usually established postnatally when core symptoms occur, including severe growth/developmental delay, coarse facial features, multiplex skeletal deformities and joint limitation1. We report a case of ML II which presented an uncommon fetal sign of transient alveolomaxillary defect (TAD) on prenatal ultrasound imaging before 28 weeks’ gestation. A 23-year-old Taiwanese primigravida was referred to our clinic for evaluation of fetal cleft lip/palate suspected on ultrasound examination at 24 weeks’ gestation. Detailed sonographic examination confirmed the presence of an alveolomaxillary defect, in which a hole in the maxilla was identified but the soft tissue of the upper lip appeared intact (Figure 1). No other associated structural abnormality was noted. Chromosome analysis revealed a normal male karyotype. The mother denied any drug or teratogen exposure and the personal and family histories of both parents were unremarkable. The pregnancy was then followed with normal serial ultrasound examinations. Unexpectedly, the alveolomaxillary defect

Unilateral Agenesis of the Internal Carotid Artery in CHARGE Syndrome

CHARGE syndrome is a multisystemic disorder comprising colobomas, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies and deafness. The CHD7 gene on chromosome 8q12.1 was recently shown to be a major gene involved in the etiology of this syndrome. We describe a girl with CHARGE syndrome who had a novel mutation of CHD7 associated with agenesis of the left internal carotid artery. She had presented with recurrent episodes of photophobia and vomiting since the age of 6 years. Since her symptoms were well controlled by cyproheptadine, migraine-like attacks were considered. CHD7 molecular confirmation in this patient provides further evidence to support the occurrence of a vascular anomaly suggested from animal models of CHARGE syndrome with molecular delineation. We report this case to emphasize the importance of neurologic signs of photophobia and to highlight the broad clinical variability in this pleiotropic disorder.

Interstitial Deletion 13q31 Associated with Normal Phenotype: Cytogenetic Study of a Family with Concomitant Segregation of Reciprocal Translocation and Interstitial Deletion

Gain or loss of a fragment in human chromosomes has been associated with abnormal phenotypes in numerous genetic disorders. However, it is also possible that lack or excess of a particular chromosomal segment is a neutral polymorphism among populations and thus does not cause obvious abnormal phenotype. In this study, conventional GTG-banded karyotyping and molecular cytogenetic analyses (including fluorescence in situ hybridization, spectral karyotyping and comparative genomic hybridization) were applied to study the genotype-phenotype correlation in a Taiwanese family, in which a concomitant segregation of del(13)(q31q31) interstitial deletion and t(13;18)(q32;p11.2) reciprocal translocation in a 2-year-old girl (the proband) was noticed. Two family members (the father and grandmother of the proband) who carried the del(13)(q31q31) but not the translocation t(13;18) both revealed a normal phenotype at adulthood. The finding, which appears novel, that interstitial deletion 13q31 could be associated with a normal phenotype, is therefore valuable in genetic counseling.

De novo Triple Segmental Aneuploid of 1p, 1q, and 4q in a Girl With Hypertrophic Cardiomyopathy, Muscle Hypotonia, and Multiple Congenital Anomalies

De novo Triple Segmental Aneuploid of 1p, 1q, and 4q in a Girl With Hypertrophic Cardiomyopathy, Muscle Hypotonia, and Multiple Congenital Anomalies Gwo-Chin Ma, Yu-Yuan Ke, Meng-Luen Lee, Long-Yen Tsao, Dong-Jay Lee, Chin-Wen Yang, Shou-Jen Kuo, Han-Yao Chiu,** and Ming Chen* Department of Genomic Medicine, Changhua Christian Hospital, Changhua, Taiwan Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan Department of Respiratory Care, Chang Jung Christian University, Tainan, Taiwan Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan Department of Obstetrics and Gynecology, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan Department of Medical Genetics, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan

Phenotype and genotype of two Taiwanese cystic fibrosis siblings and a survey of delta F508 in East Asians.

BACKGROUND Cystic fibrosis (CF) is considered to be a rare disease in Asians. We report two cases of CF in a 5-year-old girl and her newborn brother. They are of mixed parentage: a Taiwanese mother and an Australian father. METHODS A comprehensive mutational analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene was completed. Literature was reviewed for delta F508 in East Asians. RESULTS Two mutation sites were identified in the siblings. The carrier status of their parents and elder brother were also confirmed: heterozygous delta F508 mutation from the father; 13 TG repeats in the IVS8-5T from the mother. An update of delta F508 mutation reported in East Asian patients from various ethnicities is included; most of them were of mixed parentage. CONCLUSION These two cases are the first report of cystic fibrosis associated with a delta F508 mutation in a Taiwanese patient attributable to a mutation most commonly seen in Caucasians. We found that the delta F508 mutation is of western origin. Asian patients are seldom found with this mutation unless they are of mixed parentage. Our findings provide further evidence that different ethnicities have their own set of CFTR mutations.