Regular dominance of thumb ankylosis with mental retardation transmitted over 3 generations

A young girl 12 old, sent to us for obesity, and coxa-epiphysiolysis showed signs of mental retardation and bilateral thumb ankylosis. The fact that the mother was also affected by both of these signs, led to a more detailed genetic research. The latter revealed that not only the daughter, the mother, but also their own mother and may be, the sister, the grand-mother and the great-aunt of the patient had a retardation, a slight dysmorphia, a type A brachydactylia, signs of obesity and an identical ankylosis of both thumbs. This vertical inheritance, affecting apparently females only, but not associated with a high rate of miscarriage, has, it seems, never been reported. The characteristics of this family are being considered and discussed.     

Familial translocation 3/22 MAT with partial trisomy 3q (author's transl)

Two mentally retarded brothers with partial trisomy 3q show clinically similar malformations and deformities : dwarfism, bushy eyebrows, eversion of the nostrils, low inserted ears, high palate, microgeny, low hair insertion, short and broad hands with proximally inserted thumbs, clinodactylia of the 5th finger, syndactylies, mostly arch patterns on the digital pulps, muscular hypotonia, joint relaxation and cryptorchism. Both children had fits of convulsions. The younger boy showed, moreover, a perception deafness. The mother, the maternal grand-mother as well as the phenotypically normal sister of the patients revealed a balanced translocation 3/22 with a karyotype : 46,XX,t(3;22) (q25;p11).     

Teratogenic effects of diphenylhydantoin.

A child aged 24 months had multiple congenital abnormalities and delayed development. The 28-year-old mother had been treated since childhood with anticonvulsants. Her previous pregnancies had resulted in three early spontaneous abortions and one child with severe bilateral cleft lip and palate. This case report further suggests a relationship between maternal diphenylhydantoin use and fetal anomalies.     

The costs of human locomotion: Maternal investment in child transport

This article investigates maternal investment in child carrying and presents a method for determining when it is energetically advantageous for a mother to carry her child rather than force her child to walk independently. I calculate maternal and child energy consumption while walking and develop correction factors to facilitate making these energy calculations for young children. In addition, I investigate the effect of maternal burdens in addition to the child and of external nutritional support on energy consumption. Since maternal energy is a finite resource, the “decision” to carry a child or force it to walk independently is especially important. This decision can be predicted from the body mass of the mother and child and the child's age. If the mother provides all of the child's nutrition, then the mother should choose to carry her child only when the energy usage of the mother carrying the child is less than the sum of the energy used when the mother and child walk independently. The critical velocity, when the two expenditures are equal, can then be determined. Several general hypotheses are also addressed. The critical velocity of a 60 kg mother with a 4-year-old child approximately equals the average walking speed of adult humans. For a lighter mother, the critical velocity is reached when her child is 3 years old, while for heavier mother this point is not reached until her child is 6 years old. The effect of burdens in addition to the child's mass is minimal. Nutritional support of the child by agencies other than the mother decreases the age at which the mother should force the child to walk independently. In some cases, especially for the lightest mothers, it is never in the mother's best energetic interest to carry her child. Am J Phys Anthropol 107:71–85, 1998. © 1998 Wiley-Liss, Inc.     

Correlation between the cariogenic response in biofilms generated from saliva of mother/child pairs

This study aimed to correlate the cariogenic responsiveness of biofilms generated from the saliva of mothers and children. The mother–child pairs were classified according to the children’s caries levels: caries-free, early childhood caries (ECC) or severe ECC. Microcosm biofilms were grown on enamel discs for 10?days. Factors under evaluation were caries experience levels, inoculum source (mothers and children) and growth conditions including cariogenic challenge (growth medium provided with and without sucrose) and no cariogenic challenge (growth medium sucrose-free). Statistical analysis was performed with ANOVA and Tukey’s test, and the Spearman correlation test. Regular sucrose exposure resulted in a higher surface hardness change (%SHC). The correlation between biofilms formed from saliva of mother–child pairs was significant regarding pH, total aciduric microorganisms and lactobacilli counts under cariogenic challenge. Biofilm growth originating from mother–child pairs under regular sucrose exposure promoted the same cariogenic response independently of caries experience and the microbiological profile of the donors.     

Chromothripsis in Healthy Individuals Affects Multiple Protein-Coding Genes and Can Result in Severe Congenital Abnormalities in Offspring

Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8–23 breakpoint junctions across three to five chromosomes. Two mothers did not show any phenotypic abnormalities, although 3–13 protein-coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy-number changes in two children. This resulted in gene-dosage changes, which are probably responsible for the severe congenital phenotypes of these two children. In contrast, the third child, who has a severe congenital disease, harbored all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy-number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein-coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals affects reproduction and is expected to substantially increase the risk of miscarriages, abortions, and severe congenital disease.     

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.     

A silent transferrin allele in a Finnish family

In a Finnish family a silent allele was found in the transferrin (Tf) system. As determined by gel electrophoresis and immunoblotting, the Tf type of the father was CD, the mother C, and the child D. The serum Tf concentration in grandmother, mother, and child was less than 50% of normal.     

Formal genetics of esterase D (EC 3.1.1.1): evidence for a sex-phenotype association

The formal genetics of esterase D (EC 3.1.1.1) was studied in family data and mother/child pairs. A general agreement with mendelian expectations was found. However, a significant sex-phenotype association was detected in families from northwestern Portugal as well as in mother/child pairs and family data from southwestern Germany.     

Valuing mother and child health: The intrauterine environment

The paper estimates the value a mother assigns to own health relative to child health. Estimation of relative health valuation requires the decomposition of a child health improvement into its direct effect on the child's health and its indirect effect, through improvements in maternal health. Failure to distinguish the impact of the direct and indirect effects can lead to biased estimates. We consider the intrauterine environment of a pregnant mother and her unborn child, where maternal health inputs are choice variables and her health affects child health. The empirical estimates suggest that mothers value child health up to six times higher than own health, and that the relative value depends on maternal consumption patterns and household characteristics.     

A large deletion causes apparent homozygosity for the D1152H mutation in the cystic fibrosis transmembrane regulator (CFTR) gene

We report the case of a patient with an apparent homozygosity for the D1152H mutation located in exon 18 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The parents had no personal history of cystic fibrosis (CF) and referred to our laboratory after the diagnosis of fetal bowel hyperechogenicity. The proband presented with meconium ileus and normal sweat chloride test. Sequencing of the CFTR exon 18 together with quantitative genomic assays, such as real-time PCR and the multiplex ligation probe amplification (MLPA) techniques, were performed and revealed that the father was heterozygous for the D1152H mutation and the mother carried a large deletion of the CFTR gene encompassing the genomic sequence including the same mutation. The child inherited D1152H from his father and the large deletion of the CFTR gene from his mother. We suggest that D1152H likely acts as a mild mutation with a dominant effect on the severe deletion of exon 18, considering that after 3 years of clinical examinations the child shows no classical signs and symptoms of CF. Not testing for large deletions in subjects with apparent homozygosity for a mutated CFTR allele could lead to the misidentification of CFTR mutation carrier status.     

A compound-heterozygous Marfan patient: two defective fibrillin alleles result in a lethal phenotype.

We describe here the identification of defined mutations in both alleles of the fibrillin gene (FBN1) in a compound-heterozygote Marfan syndrome (MFS) child who had a very severe form of MFS resulting in death from cardiac failure at the age of 4 mo. The nonconsanguineous parents were both affected with MFS. The father's heterozygous point mutation has earlier been reported to result in W217G substitution, the mother was here shown to carry a heterozygous point mutation resulting in G2627R substitution, and the child had inherited both these mutations. The mutant FBN1 alleles were demonstrated to be transcribed with equal efficiency compared with the normal alleles, but metabolic labeling of fibroblast cultures from the child and both parents showed reduced biosynthesis and secretion of profibrillin. Also, the respective amounts of fibrillin in cell-culture media and extracellular-matrix extracts were markedly diminished, particularly in the cell cultures from father and child. In addition, immunofluorescence analysis of the cell cultures of all three family members revealed a drastically reduced amount of microfibrils, and virtually no visible fibrils could be seen in the case of the compound-heterozygote child. These findings demonstrate incomplete dominance of fibrillin mutations and underline the fatal consequences of the complete absence of normal fibrillin molecules in the microfibrils.     

Familial occurrence of 18q-

Summary An unusual segregation of the partial long arm deletion of a chromosome 18 is reported. This aberration was found in the feeble-minded mother and in her 4 daughters. The fifth child has XXY-Klinefelter's syndrome. The carriers of 18q — in this family reveal small stature, microcephaly, and mental deficiency in the range from feeble-minded to severe imbecility. Other characteristic features commonly found in patients with 18q — syndrome, as mid-face retraction, downward slanting mouth, heart defect, and atretic ear canals were not observed.     

Cell-mediated lympholysis by human maternal and neonatal lymphocytes: mother's reactivity against neonatal cells and vice versa.

Maternal reactivity in cell-mediated lympholysis (CML) against cells from her own child is, in average, half of the maternal reactivity against unrelated adult cells. This finding remains the same when cells from a newborn or from an older child are used, suggesting that the reduced maternal reactivity is based rather on the one haplotype identity between the mother and child than on the occurrence of specific maternal tolerance. Consistently, CML-capacity of the child, directed against cells of own mother, is half of the control values, again independently of the child's age.     

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.     

Population genetic data on properdin factor B (Bf) in northern Germany.

Properdin factor B phenotypes were determined in 1,112 unrelated individuals and in 151 mother/child combinations from Northern Germany. Gene frequencies were : F = 0.1960, S= 0.7905, F1 = 0.0072, S1 = 0.0063. The data of the mother/child combinations are in full accordance with the postulated gene model.     

A 3p deletion syndrome in a child with both del(3)(p25-->pter) and dup(17)(q23-->qter).

A child with monosomy for the distal part of the short arm of chromosome 3 (3p25-->pter) and trisomy for the terminal portion of the long arm of chromosome 17 (17q23-->qter) is presented. This unbalanced karyotype was derived from a balanced reciprocal 3p/17q translocation in the phenotypically normal mother. Main clinical features in the proband included growth and mental retardation, hypotonia, hirsutism, micro/brachycephaly, triangular face, synophris, broad and full nose, long philtrum, narrow upper lip, low set, posteriorly turned ears, anteriorly placed anus and congenital heart defect (Tetralogy of Fallot). Most of these clinical manifestations have been constantly reported in previous cases with terminal 3p deletion.     

Expansion of a maternally derived monoclonal T cell population with CD3+/CD8+/T cell receptor-gamma/delta+ phenotype in a child with severe combined immunodeficiency.

The diagnosis of severe combined immunodeficiency complicated by chronic graft-vs-host disease affecting liver and skin in association with engraftment of maternal T cells was established in a 5-mo-old boy. Detailed immunologic and molecular genetic studies were performed because a unique T cell phenotype was identified on initial evaluation. A major proportion of the patient's peripheral T cells expressed a CD8+ and TCR-gamma/delta+ phenotype while CD4+ T cells were virtually absent. Southern blot analysis of cell subpopulations isolated by fluorescence activated cell sorting indicated that approximately 50% of CD8+/TCR-gamma/delta+ cells were clonally related. Immunophenotyping and -genotyping also identified a clonal TCR-gamma/delta+ cell population in the child's mother. Clonal identity of these T cell populations in mother and child was demonstrated by studies using a clonspecific TCR-delta probe generated by polymerase chain reaction as well DNA sequence analysis. HLA typing and DNA fingerprinting confirmed that the child had acquired this clone diaplacentally from the mother. According to immunohistology and DNA analysis the clone was found to be virtually absent in the liver tissue suggesting that this clonal T cell population plays a minor role, if any, in the pathogenesis of the liver abnormalities in the patient. In the mother the CD8+/TCR-gamma/delta+ clone spontaneously declined to a level around 1% of PBMC several months later and has remained at this level since. We conclude that 1) a clonal expansion of TCR-gamma/delta T cells, triggered by yet unknown stimuli, may occur in otherwise healthy individuals, 2) respective T cells are able to cross the placental barrier, and 3) in an microenvironment precluding rejection, i.e., in severely immunocompromised patients, these cells may persist and even represent a significant proportion of circulating T cells.     

Characteristics of the Interaction Between Mother and Child in Early Infantile Autism (EIA)

The long-dominant psychodynamic theory of autism, which still has its supporters even today, ascribed the leading role in the formation of early infantile autism (EIA) to specific character traits of the mother: her coldness, her dominance, which paralyzed the affective life of her child and contributed to the formation of an autistic barrier. However, a more recent opinion (M. Shopler et al.) claims that such qualities of the mother are secondary inasmuch as an autistic child, displaying no instinctive attachment to the mother from birth, does not "trigger" the mother's maternal instincts.