The father of the propositus in family F had a low cobalamin concentration and low-normal TC I/HC and may thus have had mild TC I/HC deficiency, but this remains unconfirmed, as does the somewhat similar picture in the brother; their findings, like the borderline findings in the mother in family E, closely resemble the low-normal TC I/HC concentrations in the obligate heterozygote in family A (Table 1).
(a) Patient TC I/HC Plasma, Saliva, Cobalamin, pmol/L nmol/L pmol/L Family A Propositus 0 (b) 0 (b) 65 (c) Daughter (a) 169 21.5 - (c) Family B Propositus 1 (e) Absent Absent Low Propositus 2 (e) 0 (b) 0 (b) 39 Brother of both propositi (f) 98 23.1 157 Son of propositus 1 (d) 74 24.2 139 Son of propositus 2 (d) 111 19.4 127 Reference interval 165-454 6.5-98.1 140-750 (a) The propositus in family A was found during the survey to have classic severe TC I/HC deficiency in this study (lactoferrin concentrations were within the reference interval).
For the isolated Hb fractions from the propositus, the precipitation was 88% in the Hb Xo fraction and 68% in the Hb [A.sub.0] fraction after 15 min; for the hemolysate from a healthy individual, in which the Hb concentration was adjusted to that of the Hb fractions, the precipitation was 61%.
DNA analysis of the propositus revealed heterozygosity for a C[right arrow]G transversion at codon 5 of the [beta]-globin gene, which replaces proline with alanine (CCT[right arrow]GCT; 05Pro[right arrow]Ala).
(a) Patient Genotype Genotype determined determined by PCR-RFLP by sequence analysis Paternal aunt MM M[M.sub.Heerlen] Mother MZ MZ Propositus
MZ [M.sub.Heerlen]Z Sister MZ [M.sub.Heerlen]Z Niece MM [MM.sub.Heerlen] Nephew MM [MM.sub.Heerlen] Patient Phenotype Serum determined AAT, g/L by IEF (0.8-2.0) (b) Paternal aunt ND (c) ND Mother MZ 1.1 Propositus
Z 0.3 Sister Z 0.4 Niece M 1.2 Nephew M 0.9 (a) Both the DNA-based PCR-RFLP test as well as IEF yield improper results if the [M.sub.Heerlen] allele is present.
For sequencing of CD13 cDNA, whole blood was collected from the propositus
(40-year-old woman) of a family described previously (1).
Direct sequencing of the amplified DNA from the propositus
confirmed the nucleotide change from GGT to GAT at codon 69 of the [beta]-gene, which corresponds to a Gly[right arrow]Asp replacement at position 69.
It was speculated that the FVII of the propositus
, which has different activation patterns for TFs from different sources, might possess substitution of Arg 79 or Gln 304.
Serum samples were collected from the propositus
, her father, mother, paternal grandmother, and younger sister, none of whom had any particular disease, and an unrelated healthy volunteer (a 37-year-old man) as a control.
Serum ALT activity of the propositus
' parents and his brother and sisters was within reference limits.