Jun K.R.,University of Ulsan |
Jun K.R.,Genome Research Center for Birth Defects and Genetic Disorders |
Jun K.R.,Inje University |
Seo E.-J.,University of Ulsan |
And 7 more authors.
American Journal of Medical Genetics, Part A | Year: 2011
Here, we describe the clinical features of a boy with a 5.6-Mb deletion at chromosome 7p15.1-p15.3. He has mild facial anomalies, hand-foot abnormalities, hypospadias, congenital heart defects, and supernumerary nipples. This deletion was detected by array comparative genomic hybridization and verified by fluorescence in situ hybridization using BACs selected from the USCS genome browser. This deletion was not found in subsequent FISH analysis of the parental chromosomes. The deleted region contains several genes, including contiguous developmental genes on the HOXA cluster, which play a role in regulating aspects of morphogenesis during normal embryonic development. The patient's limb and urogenital features were similar to those observed in hand-foot-genital syndrome, which is caused by haploinsufficiency of HOXA13, whereas the congenital heart defect may reflect the deletion of HOXA3. We hypothesized that many clinical features of the patient were due to combined haploinsufficiency of the HOXA cluster. Our study also demonstrates the clinical usefulness of a molecular cytogenetic tool that is capable of detecting imbalances in the genome. © 2011 Wiley-Liss, Inc.
Jin H.Y.,University of Ulsan |
Heo S.-H.,Genome Research Center for Birth Defects and Genetic Disorders |
Kim Y.-M.,University of Ulsan |
Kim G.-H.,University of Ulsan |
And 3 more authors.
Hormone Research in Paediatrics | Year: 2014
Background/Aims: This study aimed to clarify the frequency, phenotypes, and molecular spectrum of DUOX2 , TPO , TSHR, and TG mutations in patients with congenital hypothyroidism (CH) with enlarged or normal-sized eutopic thyroid glands.Methods: The study cohort included 43 subjects from 41 unrelated families who had CH with eutopic thyroid glands. Mutation analyses of DUOX2 , TPO , and TSHR were performed. The functional capacities of novel missense variants of DUOX2 were verified by measuring H2O2 generation in vitro.Results: Of the 43 subjects, 23 (53.5%) had sequence variants in at least one gene. Twelve different DUOX2 variants, including seven novel variants, were identified in 20 subjects. A functional analysis of the DUOX2 variants revealed that most variants, other than p.G206V and p.H678R, caused a significant reduction in H 2 O 2 generation. Therefore, 15 subjects harbored functionally deleterious DUOX2 variants. Of these, 5 subjects had transient CH, and 10 were found to have permanent CH. Sequence variants in TSHR were identified in 5 subjects. One of the 43 subjects (2.3%) had sequence variants in two different genes.Conclusions: DUOX2 variants are a relatively common cause of CH with normal-sized or enlarged eutopic thyroid glands. Variable phenotypes were associated with partial loss of the functional activity of DUOX2 variants. © 2014 S. Karger AG, Basel.