Molecular Genetics of Lactase Deficiencies

Congenital lactase deficiency (CLD) (MIM 223000) is a rare autosomal recessive gastrointestinal disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. The CLD locus was previously assigned by linkage and linkage disequilibrium analyses on 2q21 in 19 Finnish families. In this study, the molecular background of this disorder is reported. The CLD locus was refined in 32 CLD patients in 24 families by using microsatellite and single nucleotide polymorphism (SNP) haplotypes. Mutation analyses were performed by direct sequencing. We identified 5 distinct mutations in the lactase (LCT) gene, encoding the enzyme that hydrolyzes lactose in the intestinal lumen. These findings facilitate genetic testing of CLD in clinical practice and enable genetic counseling. The present data also provide the basis for detailed characterization of the molecular pathogenesis of this disorder. Adult-type hypolactasia (MIM 223100) (lactase non-persistence, lactose intolerance) is an autosomal recessive gastrointestinal condition that is a result of a decline in the activity of lactase in the intestinal lumen after weaning. Adult-type hypolactasia is considered to be a normal phenomenon among mammals and symptoms are remarkably milder than experienced in CLD. Recently, a variant C/T-13910 was shown to associate with the adult-type hypolactasia trait, locating 13.9 kb upstream of the LCT gene. In this study, the functional significance of the C/T-13910 variant was determined by studying the LCT mRNA levels in intestinal biopsy samples in children and adults with different genotypes. RT-PCR followed by solid-phase minisequencing was applied to determine the relative expression levels of the LCT alleles using an informative SNP located in exon 1. In children, the C-13910 allele was observed to be downregulated after five years of age in parallel with lactase enzyme activity. The expression of the LCT mRNA in the intestinal mucosa in individuals with the T-13910 A-22018 alleles was 11.5 times higher than that found in individuals with the C-13910, G-22018 alleles. These findings suggest that the C/T-13910 associated with adult-type hypolactasia is associated with the transcriptional regulation of the LCT gene. The presence of the T-13910 A-22018 allele also showed significant elevation lactase activity. Galactose, the hydrolysing product of the milk sugar lactose, has been hypothesized to be poisonous to ovarian epithelial cells. Hence, consumption of dairy products and lactase persistence has been proposed to be a risk factor for ovarian carcinoma. To investigate whether lactase persistence is related to the risk of ovarian carcinoma the C/T-13910 genotype was determined in a cohort of 782 women with ovarian carcinoma 1331 individuals serving as controls. Lactase persistence did not associate significantly with the risk for ovarian carcinoma in the Finnish, in the Polish or in the Swedish populations. The findings do not support the hypothesis that lactase persistence increases the risk for ovarian carcinoma.

Studio portrait of Liselotte "Lotte" Stern nee Wallerstein.

Photograph probably taken shortly before her marriage to Alfred Stern in 1928.

The role of AIP and CDKN1B/p27Kip1 in endocrine neoplasia

Identification of genes predisposing to tumor syndromes has raised general awareness of tumorigenesis. Genetic testing of tumor susceptibility genes aids the recognition of individuals at increased risk of tumors. Identification of novel predisposing genes enables further studies concerning the classification of potential associated tumors and the definition of target patient group. Pituitary adenomas are common, benign neoplasms accounting for approximately 15% of all intracranial tumors. Accurate incidence estimation is challenging since a great portion of these adenomas are small and asymptomatic. Clinically relevant adenomas, that cause symptoms due to the expansion of the cell mass or the over-secretion of normally produced hormones, occur in approximately one of 1 000 individuals. Although the majority of pituitary adenomas are sporadic, a minority occur as components of familial syndromes, such as Multiple Endocrine Neoplasia type 1 (MEN1) and Carney complex (CNC). MEN1 syndrome is caused by germ-line mutations in the MEN1 gene, whereas most of the CNC patients carry the mutated protein kinase A (PKA) regulatory subunit-1-α (PRKAR1A) gene. Recently, other conditions predisposing to endocrine tumors have been identified: Pituitary Adenoma Predisposition (PAP) and MEN type 4 (MEN4). PAP was originally identified in a genetically homogeneous Finnish population. In a population based cohort from Northern Finland, aryl hydrocarbon receptor-interacting protein (AIP) gene mutations were found in 16% of all patients diagnosed with growth hormone (GH) producing pituitary adenoma, and in 40% of the subset of patients who were diagnosed under the age of 35 years. Since AIP mutations were originally described in a defined, homogeneous population from Northern Finland, it was relevant to study whether mutations also occur in more heterogeneous populations. In patient cohorts with different ethnic origins and variable clinical phenotypes, germ-line AIP mutations were detectable at low frequencies (range 0.8-7.4%). AIP mutation-positive patients were often diagnosed with a GH-producing adenoma at a young age, and usually had no family history of endocrine tumors. The low frequency of AIP mutations in randomly selected patients, and the lack of any family history of pituitary adenomas create a challenge for the identification of PAP patients. Our preliminary study suggests that AIP immunohistochemistry may serve as a pre-screening tool to distinguish between the AIP mutation-negative and the mutation-positive tumors. Tumors of various endocrine glands are components of MEN1 and CNC syndromes. Somatic MEN1 and PRKAR1A mutations in sporadic pituitary adenomas are rare, but occur in some of the other tumors related to these syndromes. The role of AIP mutations in endocrine neoplasia was studied and our results indicated that somatic AIP mutations are rare or non-existent in sporadic tumors of endocrine glands (0 of 111). Furthermore, germ-line AIP mutations in prolactin producing adenomas (2 of 9) confirmed the role of this pituitary tumor type in the PAP phenotype. Thyroid disorders are common in the general population, and the majority of them are sporadic. Interestingly, it has been suggested that thyroid disorders might be more common in PAP families. For this reason we studied germ-line AIP mutations in 93 index cases from familial non-medullary thyroid cancer (NMTC) families. The underlying gene or genes for familial NMTC have not been identified yet. None of the patients had any potentially pathogenic AIP mutation. This suggests that AIP is unlikely to play a role in familial NMTCs. A novel multiple endocrine syndrome was originally described in rats with phenotypic features of human MEN type 1 and 2. Germ-line mutations of cyclin-dependent kinase inhibitor 1B (CDKN1B also known as p27Kip1) gene were reported later in these rats and a germ-line mutation was also identified in one human family with MEN1-like phenotype (later named MEN4). To confirm the importance of this gene’s mutations in humans, we performed a mutation screening in MEN-like patients and in patients with pituitary adenoma. Our results indicate that CDKN1B/p27Kip1 mutations appear in a small portion of MEN1-like patients (one of 36), and that such mutations are rare or non-existent in both familial (0 of 19) and sporadic pituitary adenoma patients (0 of 50). In conclusion, this work strengthens the tumor susceptibility role of AIP and CDKN1B/p27Kip1 in endocrine neoplasia. Clarifying the PAP phenotype facilitates the identification of potential AIP mutation carriers. Genetic counseling can be offered to the relatives and follow-up of the mutation carriers can be organized, hence an earlier diagnosis is feasible.

Studio portrait of Liselotte "Lotte" Stern nee Wallerstein.

Photograph probably taken shortly before her marriage to Alfred Stern in 1928.

Paul; Montevideo, Uruguay Portraits Men

Paul was the son from a previous marriage of Hermann Judey's first wife Olga Judey nee Fischmann

Photographs from Rueckblick und Blick in die Ferne.

To view photographs from this memoir online, please use the links below. If no links are available, please contact the LBI photo archivist.

Briske Family Collection 1888-1948

26 vital documents for Rudolf Eduard Briske (birth, marriage military, etc.); 30 vital documents of ascendants of Rudolf Eduard Briske; 10 vital documents for relatives of Rudolf Eduard Briske; 4 photos of tombstones; one photo of Hans Briske.

Max Jacobsen Collection 1803-1894

Photocopies of documents: on the Schutzjude Moses Jacob during the Napoleonic Wars (1803-1813); other documents relating to Jewish life in Hamburg; graduating diploma from "Hoehere Buergerschule" (1866); excerpt from letter of Louis Jacobsen to his son living in Leedsat the occasion of the outbreak of the Prussian French War (1870); letter of G. Roemer to Louis Jacobsen (1866) after he was refused the marriage with Emilie Jacobsen; partial translation of will of Nathan Joseph living in Wittingen (1844); excerpt from letter of Emilie Heine to her son Ludwig who is a first-year medical student in Munich (1894).

Petusta pitsaan : Ruokahuollon järjestelyt kriisiaikojen Suomessa

From bark bread to pizza - Food and exceptional circumstances: reactions of Finnish society to crises of food supply This study on the food supply under exceptional circumstances lies within the nutritional, historical and social sciences. The perspective and questions come under nutrition science, but are part of social decision-making. The study focuses on the first and second world wars as well as on contemporary society at the beginning of the 21st century. The main purpose of this study is to explore how Finnish society has responded to crises and what measures it has taken to sustain institutional food services and the food supply of households. The particular study interests include the school catering and food services in hospitals during the world wars. The situation in households is reflected in the counseling work carried out by state-run or civic organisations. Interest also focuses on the action of the scientific community. The decisions made in Finland are projected onto the solutions developed in some other European countries. The study is based primarily on the archive documents and annual reports prepared by food and health care authorities. Major source materials include scientific and professional publications. The evaluation of the situation in contemporary Finnish society is based on corresponding emergency plans and guidelines. The written material is supplemented by discussions with experts. Food rationing during the WWI and WWII differed in extent, details and unity. The food intake of some population groups was occasionally inadequate both in quantity, quality and safety. The counseling of the public focused on promoting self-sufficiency, improving cooking skills and widening food habits. One of the most vulnerable groups in regard to nutrition was long-term patients in institutions. As for future development, the world wars were never-theless important periods for public food services and counseling practices. WWII was also an important period for product development in the food industry. Significant work on food substitutes was carried out by Professor Carl Tigerstedt during WWI. The research of Professors A. I. Virtanen and Paavo Simola during WWII focused on vitamins. Crises threatening societies now differ from those faced a hundred years ago. Finland is bet-ter prepared, but in many ways more vulnerable to and dependent on other actors. Food rationing is a severe means of handling the scarcity of food, which is why contemporary society relies primarily on preparedness planning. Civic organisations played a key role during the world wars, and establishing an emergency food supply remains on their agenda. Although the objective of protecting the population remains the same for nutrition, food production, and food consumption, threat scenarios and the knowledge and skill levels of citizens are constantly changing. Continuous monitoring and evaluation is therefore needed.

Deutsch-Boehm Family collection 1834-1938 Bulk: 1834-1892

The collection holds original official documents pertaining to the ancestors of Hermann Deutsch, such as his father, Hugo Deutsch, and his grandfather, Simon Deutsch, and the last will and testament of Abraham Nathan Meyer, great-grandfather of Hermann Deutsch. Also included are documents for Hermann Boehm. There is a printed obituary by Hugo Preuss for Hugo Deutsch and the copy of a 1938 document, declaring the end of the Simon Boehm company.

Jacobs family collection 1877-1900

Vital documents of the Jacobs family: marriage certificate (1907); military certificate (1899); birthday poem for Selig Loewenstein (1926); school certificates; birth certificate.

Memoirs of an immigrant and his ashtray

The memoirs were written in 1999. Childhood memories in a small town in Lower Austria. Passion for playing football (soccer). Recollections of daily life with rituals of coffeehouse visits and family dinners in the countryside. First experiences of antisemitism in the mid 1930s. Rising Nazi movement and illegal meetings in the local community. Annexation of Austria in 1938. First encounters with anti-Jewish regulations and discrimination by neighbors and acquaintances. Walter experienced severe difficulties at school and was frequently insulted and beaten up. Decision to leave school. The family was forced to leave Eggenburg soon thereafter, and the town declared itself "Judenfrei" (free of Jews). Move to Vienna, where they stayed with relatives. Walter, who had been brought up as a Catholic, suddenly saw himself confronted with orthodox Jewish people of different customs. Increasing restrictions for Jews. Walter was enrolled in a program at the Vienna Jewish community to learn carpentry. Recollections of the terror of Kristallnacht. Walter and his brother Ludwig were signed up for a children transport to England by the Quaker organization and left Vienna in December 1938. Difficult feeling to depart from their parents. Arrival in Harwige. They were taken to a camp in Lowestoft. Cultural differences. Walter and his brother were sent to a training farm in Parbold. Simple living conditions and difficult circumstances. Farm work and school lessons. Outbreak of the war. Scarce news of their parents, who tried to leave for Argentina. Walter's older brother Ludwig was sent to an internment camp in Adelaide, Australia. After two years he volunteered in the Pioneer Corps and returned to England. In 1941 their parents finally managed to emigrate to Argentina. Walter decided to join them, and in 1943 he left for Buenos Aires. During the passage on the Atlantic the ship was sunk by a German submarine. Rescue by the US Army. Continuation of his trip via New York.

Momma's arc 1930-1945

The memoirs were written in New York in 1999. Description of the childhood of Rosemarie Schink, the author's mother, in the rural area of Meuszelwitz, Thuringia, where her grandfather, Franz Harnish, was the station manager. Rosemarie Schink eloped to Amsterdam with the Dutch Jew Judah Easel in 1931. The marriage fall apart soon thereafter, and Rosemarie was taken under the wings of her father-in-law Joseph Easel. The couple stayed officially married until their divorce in 1940, and Rosemarie worked in the pension of her in-laws. She had a long affair with the German Jew Guy Weinberg from Hamburg, a married man who was living in Amsterdam and became the father of her daughter Julia. Description of the Weinberg family history. In 1941 Rosemarie Schink married the Austrian Jewish lawyer Herbert Mauthner, the eldest of three sons of Robert Mauthner, director of the Bodenbacher-Dux Railroad and Melanie Leitner, daughter of a wealthy family from Veszprem, Hungary. Mauthner family history and nobility of the Leitner family, who were admitted to the court of the Austrian Kaiser Franz Joseph.

How do you like America? 1800-1940

The memoirs were written in 2000 in California and contains some of the author's diary entries during the years of the family's emigration and reminiscences of the author's father. Detailed description of family history going back to the early 19th century. The author's grandfather Moses Stern had a rawproduct business in Gelsenkirchen, Westphalia. His father Max Stern took his graduate exam (Abitur) at the Jacobsohn boarding school in 1904 and was sent to a business school in Brussles, Belgium. Work in the family business M. Stern AG. World War One and rise of the family business with branches throughout Germany and offices in New York, London, Milan and Stockholm. Due to political unrest at the end of the war the business administration moved to Essen. Description of the family background of Beate Herzberg, the author's mother. Courtship of his parents and marriage in 1922. Birth of his sister Annelore in 1923. Martin Stern was born in 1924. Description of the family household and domestic life in a well-to-do family the 1920s. Friday visits to the synagogue and celebration of Jewish holidays. Vacations at the North sea and skiinig in the Alps. Martin attended a Jewish elementary school. Rising National Socialism. After Hitler came to power in 1933 the author's father immediately started preparations for the family's emigration, but was persuaded to stay by his family. Life under National Socialism. Martin attended Gymnasium and was one of only two Jewish students in his class. Antisemitic incidents. Private lessons in piano and Hebrew. Bar Mitzvah in 1937. Recollections of performances of the Kulturbund.

Sokolosky: A Story of a Family 1860-1990

Genealogy of Sokolosky family reaching back to their Posen origins; emigration to New Orleans, Mississippi and Texas in 1860s; further family history in USA until 1990. Contains also preface by Rabbi Malcolm H. Stern, photographes of members of Sokolosky family, of gravestones and of family documents.