New mutation versus exclusion at the alpha-1-antitrypsin locus: a multifaceted approach in a problematical paternity case

In a case of disputed paternity with overwhelming indications of fatherhood for the putative father, as supported by serological tests and biostatistical evaluation, a classical exclusion constellation was found at the alpha 1-antitrypsin (PI) locus: mother PI M1; child PI M1M3, and putative father PI M1M2. Additional studies included PI oligonucleotide phenotyping and DNA fingerprint analysis. Results from the entire data set led us to assume a rare genetic event at the paternal PI locus. Intracistronal crossing-over offered the most parsimonious explanation, and was compatible with the PI gene DNA sequence and the amino acid sequences of the molecule and its allelic forms, as well as with the experimental findings.     

False paternity exclusion in the Rh system: use of cytofluorometry analysis

In a two-men paternity testing analysis, the first putative father was definitely excluded by six blood group systems; the second one was apparently excluded in the Rh system. In fact, an analysis by flow-cytometry demonstrated that this false exclusion was due to the presence of a D--haplotype in the father and child.     

A Gc silent allele encountered in a paternity case

A father-child incompatibility only in the Gc system was detected in a paternity case tested at our laboratory. Quantitative determination revealed that the Gc level in the two individuals was less than 50% of the normal mean value. Evaluation of the probability calculation for the putative father using all other markers showed that he was the biological father with a very high probability. Thus it was concluded that a silent allele Gc*QO was transmitted from the father to the child.     

Alpha-1-antitrypsin and transferrin null alleles in the Portuguese population

In a Portuguese family, a null allele was found in the Pi system. An apparent 'exclusion' of the mother was found to be due to the presence of null alleles in mother and child. A transferrin (Tf) null allele was found in a case of disputed paternity. The mother and putative father were heterozygous for Tf null alleles and the child was homozygous (TfQ0) and presented hypotransferrinemia.     

Transferrin subtypes and variants in Germany; Further evidence for a Tf null allele

Summary Isoelectric focusing (IEF) with carrier ampholytes was used for the determination of transferrin C subtypes and transferrin B and D variants in a sample of 1125 unrelated individuals from Southern Germany. The observed TfC allele frequencies were Tf*C1=0.7872, Tf*C2=0.1365, and Tf*C3=0.0675. The rare C subtype C6 was observed twice. A new C subtype, called C10, was observed and identified by IEF with immobilized pH gradients. The rare C subtypes C4 and C8 were also studied by this method. TfB and TfD variants were found with a heterozygous frequency of 1.53%. One new TfD was found which is located between D1 and D2 and therefore named D1-2. Evidence for a Tf null allele was obtained in a child and the putative father; they were considered to be heterozygous for an allele Tf0. The theoretical exclusion rate for paternity examinations was calculated for the Tf system and found to be 17.95%.     

Three rare G-6-PD variants from Porto Alegre,Brazil

Summary Studies in 772 children and their mothers living in Porto Alegre, Brazil, disclosed three rare G-6-PD phenotypes. The first, observed in a dark mulatto, is probably identical to a variant previously found in Northeastern Brazil and was named Gd Minas Gerais-like; a white boy of German ancestry showed what seems to be Seattle-like; and a white man of Portuguese ancestry presented a previously undescribed variant that is being called Gd Porto Alegre. The allele responsible for Gd Minas Gerais may be more prevalent in Brazilian populations than was previously thought. Its estimated frequency in 214 black males from Porto Alegre is 0.005.     

Hemoglobin G San José {\text{[}}\beta _{\text{2}} {\text{(A4)Glu}} \to {\text{Gly}}\alpha _{\text{2}} {\text{],}}β thalassemia,and α thalassemia in a sicilian family

A 3-year-old child of Sicilian origin was found to have a severe form of Cooley's anemia. Investigations were extended to other members of her family. In three, a rare beta-chain structural Hb variant, Hb G San José [beta 7 (A4) Glu to Gly], was observed: in the father of the porposita heterozygosity for the abnormal Hb was found to be coexistent with beta o thalassemia; two sisters had lowered MCV and MCH values and levels of the abnormal Hb significantly lower than in other heterozygotes for Hb G San José. The alpha-chain/total beta-chain synthesis ratios suggest an alpha-thalassemic-like effect. Their mother had lowered MCV and MCH values, an Hb A2 level in the upper limit of the normal range, and a balanced alpha-chain/beta-chain synthesis ratio. Therefore, the possibility of coexistence of an alpha thalassemia trait with a beta thalassemia trait in the mother of the proposita and with Hb G San José heterozygosity in the two sisters who had lowered levels of abnormal Hb is discussed.     

A de novo recombination in the ABO blood group gene and evidence for the occurrence of recombination products

We have encountered a paternity case where exclusion of the putative father was only observed in the ABO blood group (mother, B; child, A1; putative father, O), among the many polymorphic markers tested, including DNA fingerprints and microsatellite markers. Cloning a part of the ABO gene, PCR-amplified from the trio’s genomes, followed by sequencing the cloned fragments, showed that one allele of the child had a hybrid nature, comprising exon 6 of the B allele and exon 7 of the O1 allele. Based on the evidence that exon 7 is crucial for the sugar-nucleotide specificity of A1 and B transferases and that the O1 allele is only specified by the 261G deletion in exon 6 of the consensus sequence of the A1 allele, we concluded that the hybrid allele encodes a transferase with A1 specificity, resulting, presumably, from de novo recombination between the B and O1 alleles of the mother during meiosis. Screening of random populations demonstrated the occurrence of four other hybrid alleles. Sequencing of intron VI from the five hybrid alleles showed that the junctions of the hybrid alleles were located within intron VI, the intron VI-exon 7 boundaries, or exon 7. Recombinational events seem to be partly involved in the genesis of sequence diversities of the ABO gene. Received: 25 October 1996     

Challenges to Modeling Dynamics in Developing a Developmental Understanding of Father-Child Relationships

This article discusses the challenges of theorizing and modeling father–child relationships in a developmentally sensitive context. Challenges to the creation of comprehensive theories are briefly discussed and concerns with conceptualizations of father involvement are reviewed. An alternative view of father–child relationships is garnered from meta-analytic perspectives. Affective climate, behavioral style and relational synchrony are identified as factors that always matter in father–child relationships regardless of the age of gender of the child, the context of fathering, or moderating factors.     

Characterization of a spontaneous mutation to a beta-thalassemia allele.

We have studied a nuclear family containing a single child with severe beta-thalassemia intermedia, a Greek-Cypriot mother with hematological findings of beta-thalassemia trait, and a Polish father who is hematologically normal. Since both the child and her father were heterozygous for a DNA polymorphism within the beta-globin gene, it was possible to clone and sequence the beta-globin gene identical by descent from both the child and her father. A nonsense mutation in codon 121 (GAA----TAA) was found in the beta-globin gene of the child, while the same gene from her father lacked this mutation and was normal. This mutation has not been previously observed among over 200 beta-thalassemia genes characterized in Caucasians. Since the mutation eliminates an EcoRI site in the beta-globin gene, we could show that the mutation is not present in genomic DNA of the father. To rule out germinal mosaicism, sperm DNA of the father was also digested with EcoRI, and the mutant EcoRI fragment was not observed under conditions that would detect the mutation if it were present in at least 2% of sperm cells. Routine HLA and blood group testing supported stated paternity. In addition, studies with 17 DNA probes that detect multiple allele polymorphisms increased the probability of stated paternity to at least 10(8):1. These data provide evidence that the G----T change in codon 121 of the beta-globin gene in the child is the result of a spontaneous mutation that occurred during spermatogenesis in a paternal germ cell.     

Paracentric inversion of Yq and review of the literature

We report on the second prenatal diagnosis of familial paracentric inversion of the long arm of Y chromosome [46, X, inv(Y)(q11.2q12)]. The anomaly was detected through an amniocentesis performed because of advanced maternal age. The inversion has been detected by standard GTG banding methods and better characterized by FISH with painting probe and specific satellite probes DYZ1 and DYZ3. The inversion derived from phenotypically normal father. Pregnancy was uneventful and an healthy child was born. We discuss the issue concerning genetic prenatal counselling of this rare condition and we report the clinical follow up of the child.     

Über die Verwendung des Pseudocholinesterase-Polymorphismus im Paternitätsgutachten

Zusammenfassung Pseudocholinesterase-Varianten können heute ohne großen Aufwand routinemäßig bestimmt werden. Es wurde deshalb die Frage geprüft, ob dieser Polymorphismus in der Paternitätsbegutachtung verwendet werden kann.Wegen der ungünstigen Genverteilung ist nur in sehr wenigen Fällen eine zusätzliche Information zu erwarten. Stimmen Kind und fraglicher Vater indessen in einer seltenen Variante überein, so ist der Hinweiswert sehr hoch (Essen-Möller-Ansatz). Die Chance, von der Vaterschaft ausgeschlossen zu werden, liegt für zu Unrecht bezichtigte Männer bei etwa 1,5%. Dazu werden eigene Untersuchungen mitgeteilt.

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Today, pseudocholine-esterase variants can be routinely differentiated without very specialized technical equipment. Therefore this well known polymorphism should be taken into consideration in paternity cases.In view of the distribution of gene frequencies, however, additional information is to be expected in very few cases only. If child and suspected father have a rare variant in common the likelihood for this man to be the father is very high (Essen-Möller's formula). The chance for wrongly accused men to be excluded is in the range of 1,5%. Some own observations are discussed.

     

A rare case of monosomy 18p: translocation between chromosomes 18 and 21

A rare case of monosomy 18p with molecular cytogenetic characterization of 18;21 whole arm translocation is presented. An 8-year-old gril with mental deficiency and growth deficiency was the child of a 45-year-old healthy mother and 50-year-old nonconsanguineous father with unremarkable prenatal history. She had a round face, flat nasal bridge, micrognathia and hypotonia. Cytogenetic studies revealed de novo 45,XX,del(18)t(18;21) karyotype, which was confirmed by fluorescence in situ hybridization (FISH).     

Complexities in Research on Fathering: Illustrations from the Tufts Study of Young Fathers

Theory and research suggest that the transition to parenthood is a major life transition, and that adaptation to the parenting role is influenced by a complex set of factors, including the relationship with the child's mother, family of origin, and how the father is situated within sociocultural contexts. The father–]mother relationship is particularly important for men making the transition to fatherhood. This study examined patterns of fathering among young fathers (15–24 years) and investigated how fathers' relationships with the mothers of their young children (infants and toddlers) were related to fathering. In general, higher quality father–mother relationships were related to greater father involvement with children; when mothers were perceived as barriers to involved fathering fathers also had less accurate and adaptive parenting knowledge, attitudes, and behavior. Person-centered analyses revealed quite complex relations between father–mother relationships and father–child interaction. One pattern showed strong positive father–mother relationships associated with a disengaged pattern of father–child interaction, while another pattern showed sensitive and positive father–child engagement in the context of negative or distant father–mother relationships. Four patterns of association between fathering and mother–father relationships were demonstrated. Results highlight the complexity of understanding fathering and family relationships among young fathers.     

Human complement C81 (C8 A) polymorphism: detection and segregation of new variants

In addition to the earlier detected C81(A) rare variants A1, A2 (now A3) and B1 (now B2), six new rare variants (C81 A2 new, A4, A5, A6, M1 and B1new) are described within the polymorphism of the eighth component of human complement (- chain subunit). Except for A3, all rare C81 A variants are only detected by isoelectric focusing, and not by SDS polyacrylamide gel electrophoresis (PAGE), in the - subunit. In one individual out of approximately 700 individuals studied, a reversed position of the common allele (B vs A) was observed by SDS PAGE and the isofocusing technique. The segregation of A1, A3 and A4 could be followed in putative father/child combinations.     

A new variant of chromosome 16

Summary A new variant of chromosome 16 with an additional C-band negative segment in the proximal region of the short arm is described. This variant chromosome was found in four cases, two of which were detected prenatally. In three probands the variant chromosome 16 was inherited from a phenotypically normal father.     

Iminoglycinuria in a child in Czechoslovakia

Summary The child with iminoglycinuria is in our observation. Hyperprolinuria was seen at 5 months by screening program. The child was repeatedly examined in the hospital and was seen last time at 16 months. IQ was 67, in the urine were excessive amounts of glycine, proline a hydroxyproline. In the blood aminoacids were in normal levels. In the child was noticed the same increase of proline in the blood as in the control child of the same age following loading test with L-proline, indicating normal intestinal absoption. Both parents and father's sister's 2-year-old mentally retarded child exhibit excessive glycinuria. The father, his sister, father's father, and grandfather are partialy, congenitaly deaf.     

Occult HBV Infection May Be Transmitted through Close Contact and Manifest as an Overt Infection

The importance of transmission of occult HBV infection (OBI) via transfusion, organ transplantation and hemodialysis has been widely recognized. However, data regarding the transmission of OBI through close contact remain limited. In this study, serum samples were obtained from a child and his parents. The child had received the standard vaccination regimen at birth and produced protective antibody. Sera were tested for HBV serological markers. Nested PCR assays were used to detect HBV DNA and the amplicons were cloned and their sequences subjected to phylogenetic analysis. The results showed that both parents had occult infections while the child had an overt infection. Twelve, eleven and nine clones, from the father, mother and son, respectively, were sequenced. Serotypes adrq+, ayw1, ayw and ayr were found in the father and ayw1, adw2 and adwq+ in the mother; adrq+ was the only serotype in son. Genotype B, subgenotype C2 and a recombinant were identified in the father and genotype B, subgenotype C5 and three recombinants were found in the mother. Subgenotype C2 was the only genotype identified in the child. A phylogenetic tree showed that all of the child’s sequences and most of the father’s sequences clustered together. However, none of mother’s sequences clustered with those of the child. The surface gene from the child and his father had the same amino acid substitution pattern (T118K, T123N and G145A). We concluded that the father was the source of the son’s HBV infection, suggesting that occult HBV infection may be transmitted through close contact and manifest as an overt infection.     

Asp187Asn mutation of gelsolin in an American kindred with familial amyloidosis,Finnish type (FAP IV)

Familial amloidosis, Finnish type (FAP IV) was identified clinically in an American kindred with Scandinavian ancestry. A polymerase chain reaction (PCR)-based DNA diagnostic assay was used to identify a G-to-A mutation at position 654 of the gelsolin cDNA (G654A) in this family. Molecular diagnostic testing demonstrated the mutation in individuals in three generations — the clinically affected proband, her deceased clinically affected father, and her presumably affected presymptomatic child. This report represents a rare example of FAP IV and the G654A mutation identified in a family outside Finland. The disease-associated haplotype was similar to that observed in Finnish FAP IV families (suggesting common distant ancestry).