Multiple endocrine neoplasis type 2A (MEN2A) is one of several kinds of cancers that appear to be inherited in an autosomally dominant fashion. We have assigned the MEN2A locus to chromosome 10 by linkage with a new DNA marker (D10S5). The linkage led us to investigate other chromosome 10 markers and demonstrate linkage between the disease locus and the interstitial retinol-binding protein (IRBP) gene. The D10S5 locus was sublocalized to 10q21.1 by hybridization in situ and the IRBP gene to p11.2----q11.2 with a secondary site at q24----q25. The linkages were established using 292 members of five families, three different restriction fragment length polymorphisms (RFLPs) at D10S5 and two RFLPs recognized by the IRBP probe. The recombination frequencies from pairwise linkage analysis between the disease and two marker loci D10S5 and IRBP were 0.19 and 0.11, with maximum lod scores of 3.6 and 8.0 respectively. Ordering of the three loci by multipoint analysis placed the IRBP gene approximately midway between the disease and D10S5 loci.

We describe a family in which two males and seven females have brown pigmentation of the skin. In the females, the type and distribution of the pigmentation mimicked incontinentia pigmenti; in the males, the pattern was reticulate. The histological appearance was the same in both sexes with amyloid deposits in the papillary dermis, melanin in the basal layer, and slight hyperkeratosis. The females were otherwise normal. Both males had thrived poorly as infants but had survived. One had severe gastroenteritis with blood in the stools starting at the age of three weeks followed by seizures, hemiplegia, and developmental delay; the other had recurrent pneumonia throughout life, a urethral stricture, inguinal herniae, and near-blindness from amyloid deposition in the cornea. Five other males in the family had had severe illnesses. Two died of pneumonia by three months. One died at three months from colitis. Both remaining boys had colitis as infants, failed to thrive, and developed recurrent pneumonia from which one died at three years. We think all of these relatives had the same disease carried by a single gene with pleiotropic effects. The most likely form of inheritance is X-linked.

Family data for 2,645 probands from a Canadian Register have been genetically analyzed.Study of 173 children from matings in which the diabetic is married to a diabetic, and of 13,009 first degree relatives of diabetics, suggests that the hereditary basis for diabetes is multifactorial.There was a marked excess of diabetics among first degree relatives of probands whose age of onset was less than twenty years, over that among relatives of probands with late age of onset. This finding suggests an accumulation of "high risk" factors in families in which the proband had early age of onset. The compatability of multifactorial inheritance with recent physiological and biochemical findings is discussed.

38 genetically determined marker systems were examined in blood samples obtained from a relatively isolated population of Eskimos living in the Eastern Canadian Arctic. 2,3-DPGM, sGOT, sGPT, PGM_1; 6PGD, AcP, E₂ cholinesterase, haptoglobin, Gm, Inv, and HL-A were found to exist in polymorphic form, while no variation of the remaining 27 markers was detected in the population. The 2,3-DPGM 2–1 phenotype, which has hitherto been considered to be a rare phenotype, occurred in 3.6% of the individuals studied. One previously undescribed rare variant sGPT 5–1 was detected. Comparisons of the data for circumpolar populations indicate that the PGM²₁ allele frequencies form a gradient of increasing magnitude from west to east in Arctic populations; a suggestion of a decreasing gradient of red cell acid phosphatase P^aallele frequencies was found from west to east in these populations. Approximately 6% of the genes in the Igloolik gene pool appeared to be Caucasoid. The incidence of polymorphisms and the average degree of heterozygosity in this relatively isolated population were not found to differ statistically from the corresponding estimates for a large random mating population with little inbreeding.

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