Fine mapping of Hyplip1 and the human homolog, a potential locus for FCHL.

Familial combined hyperlipidemia (FCHL) is a common genetic dyslipidemia predisposing to premature coronary heart disease (CHD). We previously identified a locus for FCHL on human Chromosome (Chr) 1q21-q23 in 31 Finnish FCHL families. We also mapped a gene for combined hyperlipidemia (Hyplip1) to a potentially orthologous region of mouse Chr 3 in the HcB-19/Dem mouse model of FCHL. The human FCHL locus was, however, originally mapped about 5 Mb telomeric to the synteny border, the centromeric part of which is homologous to mouse Chr 3 and the telomeric part to mouse Chr 1. To further localize the human Hyplip1 homolog and estimate its distance from the peak linkage markers, we fine-mapped the Hyplip1 locus and defined the borders of the region of conserved synteny between human and mouse. This involved establishing a physical map of a bacterial artificial chromosome (BAC) contig across the Hyplip1 locus and hybridizing a set of BACs to both human and mouse chromosomes by fluorescence in situ hybridization (FISH). We narrowed the location of the mouse Hyplip1 gene to a 1.5-cM region that is homologous only with human 1q21 and within approximately 5-10 Mb of the peak marker for linkage to FCHL. FCHL is a complex disorder and this distance may, thus, reflect the well-known problems hampering the mapping of complex disorders. Further studies identifying and sequencing the Hyplip1 gene will show whether the same gene predisposes to hyperlipidemia in human and mouse.

A single PCR marker in strong allelic association with the infantile form of neuronal ceroid lipofuscinosis facilitates reliable prenatal diagnostics and disease carrier identification.

The infantile form of neuronal ceroid lipofuscinosis (INCL) is a progressive encephalopathy in children < 2 years old. The disease is one of the Finnish diseases, enriched in this genetically isolated population. The gene responsible for INCL has been recently assigned to the short arm of human chromosome 1. Here we describe DNA-based prenatal and carrier diagnostics using a highly polymorphic marker (HY-TM1) which demonstrates a strong allelic association to the disease locus. 88% of Finnish INCL patients were observed to have the same affected genotype, suggesting that one major CLN1 mutation is enriched in this population. In contrast, all the non-Finnish INCL patients had different allele combinations.

Fine-needle aspiration biopsy of liver hemangioma.

The results of 36 consecutive fine-needle aspiration biopsies of liver hemangiomas at two University Hospitals from the years 1981-1988 are described. The sizes of the lesions were 1 to 15 cm. Six patients had malignant disease, and liver metastasis was considered possible. In 2 cases the chief complaint was related to liver enlargement, and 28 patients had other abdominal symptoms. The aspiration was performed to confirm a suggested hemangioma in 18 and because of inconclusive findings at imaging in 18 cases. The aspirations were performed with sonographic guidance using 0.7 to 0.8 mm outer diameter needles. Cellular material from a hemangioma was obtained in 21 cases; only blood was aspirated in 5 cases. Hepatocytes were seen among abundant blood cells in 10, and some fibroblasts in 5 cases. One patient had significant bleeding that was treated with a transfusion of two units of blood. Nine patients were treated surgically, and histologic samples confirmed the diagnosis of hemangioma. None of the 27 non-operated patients showed progression of the liver lesion at 3 to 48 months follow-up. Fine-needle aspiration biopsy is helpful in the diagnosis of liver hemangioma. Confusion with malignancy is unlikely. Further experience will show the frequency of complications.