New Mutations of the ID1 Gene in Acute Myeloid Leukemia Patients.

OBJECTIVES: Overexpression of the inhibitor of DNA binding 1 (ID1) protein is found in many types of cancer. In acute myeloid leukemia (AML), the expression of ID1 is induced by abnormal tyrosine kinases, such as FLT3 and BCR-ABL. High level expression of ID1 is associated with poor prognosis in young patients. We aimed to explore the ID1 mutation and its prognosis in AML patients. METHODS: Two hundred and sixty-three AML patients were included. Cytogenetic results and ID1 mutation were compared. The ID1 gene was amplified by nested PCR, and the mutation was identified by direct sequencing. RESULTS: Four new ID1 mutations (G40C, A124G, A230G, A349G) were identified in the normal karyotype patients. The A349G mutation, located in the nuclear export signal domain of the ID1 protein, was predicted by the in silico method as a damaged protein. Meanwhile, another new mutation, A290G, found in cases with 11q23 deletion, corresponded to the amino acid 97 in the helix 1 position of the ID1 protein. It could interfere with the dimerization of ID1 and EST-1, leading to a disruption of cell proliferation. CONCLUSIONS: In this study, we found 5 mutations in 260 AML patients. ID1 mutations were not commonly observed in AML. This may differ in other hematologic malignancies. Further studies in other types of hematologic malignancy will help to clarify the importance of ID1 mutations. © 2015 S. Karger AG, Basel.

Van der Woude syndrome with sensorineural hearing loss, large craniofacial sinuses, dental pulp stones, and minor limb anomalies: report of a four-generation Thai family.

A four-generation Thai family affected with Van der Woude syndrome is reported. The disorder appeared to be originally inherited from a person who was half Thai and half Pakistani. The lip lesions found in this family were varied and did not appear to be related to other phenotypes. There were some clinical manifestations possibly specific for the condition in this family. They included sensorineural hearing loss, prominent frontal bone, large frontal/sphenoidal/maxillary sinuses with increased mastoid air cells, long tooth roots, dental pulp stones, ankyloglossia, brachydactyly of hands, brachyphalangy, and hyperphalangy of toes, and single flexion crease of the fifth fingers. Fluorescence in situ hybridization analysis revealed no visible deletion at a 1q32-41 region.

Contiguous gene syndrome of holoprosencephaly and hypotrichosis simplex: association with an 18p11.3 deletion.

We report a patient with a unique combination of features, including microcephaly; mental retardation; poorly developed frontal lobes; hypoplastic pituitary gland; hypothyroidism; alopecia universalis; single maxillary central incisor; taurodontism; median palatal ridge; longitudinally grooved nails; and scoliosis. His unbalanced karyotype was found to be 45,XY,der(15;18)(q10;q10). The constellation of anomalies appears to represent a contiguous gene syndrome caused, at least in part, by deletion of TGIF and the gene responsible for hereditary hypotrichosis simplex. The phenotype of our patient differs other reported patients with del(18p). Possible explanations include (1) the effects of a different deleted region, (2) a positional effect caused by a gene close by, or (3) by interruption of a different gene resulting from chromosomal translocation.