title: Clinical and genetic analysis of Korean patients with Cornelia de Lange syndrome: two novel NIPBL mutations.
abstract: Cornelia de Lange syndrome (CdLS; OMIM #122470) is a multiple congenital anomaly with characteristic facial features, growth delay, mental retardation, limb defects, behavioral problems, ocular and hearing impairments, and gastrointestinal or cardiac abnormalities. Although the NIPBL gene has been identified as a causative gene for CdLS, there has hitherto been no genetically confirmed case of CdLS in Korea. Herein, we report a clinical and genetic analysis of three Korean patients with clinical features consistent with CdLS. A male neonate had distinctive facial features, malformations of the upper extremities, genital abnormalities, and bilateral hearing loss, while a 6-yr-old boy and a 10-yr-old girl had distinctive facial features, short stature, and mental retardation. There were no chromosomal abnormalities in the three children. Sequence analysis of the NIPBL gene revealed three novel NIPBL variations including c.6108+2T>C, c.4028A>C (p.His1343Pro), and c.218C>T (p.Ser73Leu) in each patient, respectively. The first two variations appear to be de novo mutations causing CdLS in the patients because they are absent in the patients' parents. The p.Ser73Leu variation, however, seems to be a polymorphism since it is found both in the patient and in her asymptomatic mother. To the best of our knowledge, this is the first report of genetically confirmed cases of CdLS in Korea and extends the mutation spectrum of the NIPBL gene.
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyung-Doo
authors.initials: HD
authors.lastname: Park
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Woo Taek
authors.initials: WT
authors.lastname: Kim
authors.forename: Jin-Kyung
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D003635:De Lange Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007723:Korea; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D018797:Cell Cycle Proteins; C487465:NIPBL protein, human; D011506:Proteins