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Chung Lee, MD

  • Chung Un Lee

Specialties

Clinical Genetics

Work and Education

Professional Education

University of Illinois at Chicago, Chicago, IL, 5/11/2008

Internship

Kaiser Permanente Medical Center - Oakland, Oakland, CA, 6/30/2009

Residency

Kaiser Permanente Medical Center - Oakland, Oakland, CA, 6/30/2011

University of California, San Francisco (UCSF), San Francisco, CA, 6/30/2013

Fellowship

University of California, San Francisco (UCSF), San Francisco, CA, 6/30/2014

Board Certifications

Clinical Biochemical Genetics, American Board of Medical Genetics and Genomics

Clinical Genetics, American Board of Medical Genetics and Genomics

Pediatrics, American Board of Pediatrics

Services

Genetics

All Publications

Biochemical characteristics of newborns with carnitine transporter defect identified by newborn screening in California. Molecular genetics and metabolism Gallant, N. M., Leydiker, K., Wilnai, Y., Lee, C., Lorey, F., Feuchtbaum, L., Tang, H., Carter, J., Enns, G. M., Packman, S., Lin, H. J., Wilcox, W. R., Cederbaum, S. D., Abdenur, J. E. 2017

Abstract

Carnitine transporter defect (CTD; also known as systemic primary carnitine deficiency; MIM 212140) is due to mutations in the SLC22A5 gene and leads to extremely low carnitine levels in blood and tissues. Affected individuals may develop early onset cardiomyopathy, weakness, or encephalopathy, which may be serious or even fatal. The disorder can be suggested by newborn screening. However, markedly low newborn carnitine levels can also be caused by conditions unrelated to CTD, such as the low carnitine levels often associated with normal pregnancies and some metabolic disorders occurring in the mother. In order to clarify the biochemical characteristics most useful for identification of CTD in newborns, we examined California Department of Public Health newborn screening data for CTD from 2005 to 12 and performed detailed chart reviews at six metabolic centers in California. The reviews covered 14 cases of newborn CTD, 14 cases of maternal disorders (CTD, 6 cases; glutaric aciduria, type 1, 5; medium-chain acyl CoA dehydrogenase deficiency, 2; and cobalamin C deficiency, 1), and 154 false-positive cases identified by newborn screening. Our results show that newborns with CTD identified by NBS exhibit different biochemical characteristics, compared to individuals ascertained clinically. Newborns with CTD may have NBS dried blood spot free carnitine near the lower cutoff and confirmatory plasma total and free carnitine levels near the normal lower limit, particularly if obtained within two weeks after birth. These findings raise the concern that true cases of CTD may exist that could have been missed by newborn screening. CTD should be considered as a possible diagnosis in cases with suggestive clinical features, even if CTD was thought to be excluded in the newborn period. Maternal plasma total carnitine and newborn urine total carnitine values are the most important predictors of true CTD in newborns. However, biochemical testing alone does not yield a discriminant rule to distinguish true CTD from low carnitine in newborns due to other causes. Because of this biochemical variability and overlap, molecular genetic testing is imperative to confirm CTD in newborns. Additionally, functional testing of fibroblast carnitine uptake remains necessary for cases in which other confirmatory testing is inconclusive. Even with utilization of all available diagnostic testing methods, confirmation of CTD ascertained by NBS remains lengthy and challenging. Incorporation of molecular analysis as a second tier step in NBS for CTD may be beneficial and should be investigated.

View details for DOI 10.1016/j.ymgme.2017.06.015

View details for PubMedID 28711408

Molecular and clinical spectra of FBXL4 deficiency. Human mutation El-Hattab, A. W., Dai, H., Almannai, M., Wang, J., Faqeih, E. A., Al Asmari, A., Saleh, M. A., Elamin, M. A., Alfadhel, M., Alkuraya, F. S., Hashem, M., Aldosary, M. S., Almass, R., Almutairi, F. B., Alsagob, M., Al-Owain, M., Al-Sharfa, S., Al-Hassnan, Z. N., Al Rahbeeni, Z., Al-Muhaizea, M. A., Makhseed, N., Foskett, G. K., Stevenson, D. A., Gomez-Ospina, N., Lee, C., Boles, R. G., Schrier Vergano, S. A., Wortmann, S. B., Sperl, W., Opladen, T., Hoffmann, G. F., Hempel, M., Prokisch, H., Alhaddad, B., Mayr, J. A., Chan, W., Kaya, N., Wong, L. C. 2017

Abstract

F-box and leucine-rich repeat protein 4 (FBXL4) is a mitochondrial protein whose exact function is not yet known. However, cellular studies have suggested that it plays significant roles in mitochondrial bioenergetics, mitochondrial DNA (mtDNA) maintenance, and mitochondrial dynamics. Biallelic pathogenic variants in FBXL4 are associated with an encephalopathic mtDNA maintenance defect syndrome that is a multisystem disease characterized by lactic acidemia, developmental delay, and hypotonia. Other features are feeding difficulties, growth failure, microcephaly, hyperammonemia, seizures, hypertrophic cardiomyopathy, elevated liver transaminases, recurrent infections, variable distinctive facial features, white matter abnormalities and cerebral atrophy found in neuroimaging, combined deficiencies of multiple electron transport complexes, and mtDNA depletion. Since its initial description in 2013, 36 different pathogenic variants in FBXL4 were reported in 50 affected individuals. In this report, we present 37 additional affected individuals and 11 previously unreported pathogenic variants. We summarize the clinical features of all 87 individuals with FBXL4-related mtDNA maintenance defect, review FBXL4 structure and function, map the 47 pathogenic variants onto the gene structure to assess the variants distribution, and investigate the genotype-phenotype correlation. Finally, we provide future directions to understand the disease mechanism and identify treatment strategies. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/humu.23341

View details for PubMedID 28940506

Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas NATURE GENETICS Piotrowski, A., Xie, J., Liu, Y. F., Poplawski, A. B., Gomes, A. R., Madanecki, P., Fu, C., Crowley, M. R., Crossman, D. K., Armstrong, L., Babovic-Vuksanovic, D., Bergner, A., Blakeley, J. O., Blumenthal, A. L., Daniels, M. S., Feit, H., Gardner, K., Hurst, S., Kobelka, C., Lee, C., Nagy, R., Rauen, K. A., Slopis, J. M., Suwannarat, P., Westman, J. A., Zanko, A., Korf, B. R., Messiaen, L. M. 2014; 46 (2): 182-?

Abstract

Constitutional SMARCB1 mutations at 22q11.23 have been found in 50% of familial and <10% of sporadic schwannomatosis cases. We sequenced highly conserved regions along 22q from eight individuals with schwannomatosis whose schwannomas involved somatic loss of one copy of 22q, encompassing SMARCB1 and NF2, with a different somatic mutation of the other NF2 allele in every schwannoma but no mutation of the remaining SMARCB1 allele in blood and tumor samples. LZTR1 germline mutations were identified in seven of the eight cases. LZTR1 sequencing in 12 further cases with the same molecular signature identified 9 additional germline mutations. Loss of heterozygosity with retention of an LZTR1 mutation was present in all 25 schwannomas studied. Mutations segregated with disease in all available affected first-degree relatives, although four asymptomatic parents also carried an LZTR1 mutation. Our findings identify LZTR1 as a gene predisposing to an autosomal dominant inherited disorder of multiple schwannomas in 80% of 22q-related schwannomatosis cases lacking mutation in SMARCB1.

View details for DOI 10.1038/ng.2855

View details for Web of Science ID 000331208300016

View details for PubMedID 24362817

View details for PubMedCentralID PMC4352302

Homozygosity for a FBN1 missense mutation causes a severe Marfan syndrome phenotype CLINICAL GENETICS HOGUE, J., Lee, C., JELIN, A., Strecker, M. N., Cox, V. A., Slavotinek, A. M. 2013; 84 (4): 392-393

View details for DOI 10.1111/cge.12073

View details for Web of Science ID 000324297800018

View details for PubMedID 23278365

The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP ORPHANET JOURNAL OF RARE DISEASES Nikkel, S. M., Dauber, A., de Munnik, S., Connolly, M., Hood, R. L., Caluseriu, O., Hurst, J., Kini, U., Nowaczyk, M. J., Afenjar, A., Albrecht, B., Allanson, J. E., Balestri, P., Ben-Omran, T., Brancati, F., Cordeiro, I., da Cunha, B. S., Delaney, L. A., Destree, A., Fitzpatrick, D., Forzano, F., Ghali, N., Gillies, G., Harwood, K., Hendriks, Y. M., Heron, D., Hoischen, A., Honey, E. M., Hoefsloot, L. H., Ibrahim, J., Jacob, C. M., Kant, S. G., Kim, C. A., Kirk, E. P., Knoers, N. V., Lacombe, D., Lee, C., Lo, I. F., Lucas, L. S., Mari, F., Mericq, V., Moilanen, J. S., Moller, S. T., Moortgat, S., Pilz, D. T., Pope, K., Price, S., Renieri, A., Sa, J., Schoots, J., Silveira, E. L., Simon, M. E., Slavotinek, A., Temple, I. K., van der Burgt, I., de Vries, B. B., Weisfeld-Adams, J. D., Whiteford, M. L., Wierczorek, D., Wit, J. M., Yee, C. F., Beaulieu, C. L., White, S. M., Bulman, D. E., Bongers, E., Brunner, H., Feingold, M., Boycott, K. M. 2013; 8

Abstract

Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome.Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations.This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.

View details for DOI 10.1186/1750-1172-8-63

View details for Web of Science ID 000319314600001

View details for PubMedID 23621943

View details for PubMedCentralID PMC3659005