DNAI1 mutations explain only 2% of primary ciliary dykinesia.

Background: Primary ciliary dyskinesia (PCD) is a rare recessive hereditary disorder characterized by dysmotility to immotility of ciliated and flagellated structures. Its main symptoms are respiratory, caused by defective ciliary beating in the epithelium of the upper airways (nose, bronchi and paranasal sinuses). Impairing the drainage of inhaled microorganisms and particles leads to recurrent infections and pulmonary complications.

Split-hand/split-foot malformation 3 (SHFM3) at 10q24, development of rapid diagnostic methods and gene expression from the region.

Split-hand/split-foot malformation (SHFM, also called ectrodactyly) is a clinically variable and genetically heterogeneous group of limb malformations. Several SHFM loci have been mapped, including SHFM1 (7q21), SHFM2 (Xq26), SHFM3 (10q24), SHFM4 (3q27) and SHFM5 (2q31). To date, mutations in a gene (TP63) have only been identified for SHFM4.

Molecular characterization of the spectrum of genomic deletions in the mismatch repair genes MSH2, MLH1, MSH6, and PMS2 responsible for hereditary nonpolyposis colorectal cancer (HNPCC).

A systematic search by Southern blot analysis in a cohort of 439 hereditary nonpolyposis colorectal cancer (HNPCC) families for genomic rearrangements in the main mismatch repair (MMR) genes, namely, MSH2, MLH1, MSH6, and PMS2, identified 48 genomic rearrangements causative of this inherited predisposition to colorectal cancer in 68 unrelated kindreds. Twenty-nine of the 48 rearrangements were found in MSH2, 13 in MLH1, 2 in MSH6, and 4 in PMS2. The vast majority were deletions, although one previously described large inversion, an intronic insertion, and a more complex rearrangement also were found.

Trisomy 13 due to rea(13q;13q) is caused by i(13) and not rob(13;13)(q10;q10) in the majority of cases.

We have used 20 PCR-based DNA polymorphisms to determine whether trisomy 13 due to de novo rea(13q;13q) in six cases is caused by translocation (13q;13q) or isochromosome (13q;13q); to determine the parental origin of the rearrangements and the mechanisms of formation. The six probands were three liveborn children with clinical features characteristic of Patau's syndrome and three fetuses diagnosed prenatally by amniocentesis or CVS. Five cases were isochromosomes with two identical q arms, one of maternal and four of paternal origin.

A genomic rearrangement resulting in a tandem duplication is associated with split hand-split foot malformation 3 (SHFM3) at 10q24.

Split hand-split foot malformation (SHFM) is characterized by hypoplasia/aplasia of the central digits with fusion of the remaining digits. SHFM is usually an autosomal dominant condition and at least five loci have been identified in humans. Mutation analysis of the DACTYLIN gene, suspected to be responsible for SHFM3 in chromosome 10q24, was conducted in seven SHFM patients.

Prostate cancer is part of the hereditary non-polyposis colorectal cancer (HNPCC) tumor spectrum.

The recognized urologic tumor spectrum in hereditary non-polyposis colon cancer includes ureteral and renal pelvis malignancies. Here, we report a family in which the proband, who had three metachronous adenocarcinomas of the colon and rectum (at ages 54, 57, and 60), presented with an adenocarcinoma of the prostate at age 61. Immunohistochemical (IHC) staining of colonic, rectal, and prostatic tumor tissues demonstrated lack of expression of both MSH2 and MSH6.

Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD; MIM 242650) is an autosomal recessive disorder of ciliary dysfunction with extensive genetic heterogeneity. PCD is characterized by bronchiectasis and upper respiratory tract infections, and half of the patients with PCD have situs inversus (Kartagener syndrome). We characterized the transcript and the genomic organization of the axonemal heavy chain dynein type 11 (DNAH11) gene, the human homologue of murine Dnah11 or lrd, which is mutated in the iv/iv mouse model with situs inversus.