Tirza Cohen

Amelogenesis imperfecta among Israeli Jews and the description of a new type of local hypoplastic autosomal recessive amelogenesis imperfecta

Amelogenesis imperfecta (AI) was detected in nine of 70,359 school children surveyed, a prevalence approximating 1:8,000. Of these cases, eight were the hypoplastic type and one the snow-capped hypomaturation type. Family studies demonstrated that hypoplastic AI was an autosomal dominant trait in two children and an autosomal recessive in six. Of three additional families referred to our clinic, two had autosomal recessive hypoplastic AI and one the hypocalcified type, inherited as an autosomal dominant trait. In four families, a new type of local hypoplastic autosomal recessive AI was observed, characterized by horizontal pitting and grooving more pronounced in the middle third of the crowns of most teeth in both dentitions.

Hypodontia: a polygenic trait--a family study among Israeli Jews.

A high prevalence of hypodontia was detected among 820 first degree relatives of 305 probands and there was an increased risk if a second family member was affected. Hypodontia is a common trait in the population, and a deviation from normal sex ratio was observed in those affected. These results suggest a polygenic mode of inheritance.

Scrotal tongue and geographic tongue: Polygenic and associated traits☆

The familial nature of scrotal and geographic tongue was investigated in parents and siblings of 156 probands having these conditions. The prevalence in parents and siblings was significantly higher than that in the control populations. The prevalence in sibilings from families in which at least one parent was also affected was significantly higher than that in siblings from families in which neither parent was affected. The prevalence of scrotal tongue alone in siblins was similar irrespective of the condition in the proband. The prevalence of geographic tongue alone was highest in siblins of probands having only geographic tongue. A polygenic mode of inheritance with some genes common to both conditions is suggested.

The ATC (ataxia-telangiectasia complementation group C) locus localizes to 11q22–q23

The multisystem autosomal recessive disease ataxia-telangiectasia (A-T) is determined by several genes, as evidenced by the existence of four complementation groups in this disorder. Using linkage analysis, the ATA (A-T complementation group A) gene was previously localized to chromosome 11, region q22-q23. Analysis of the segregation of RFLP markers from this region in a Jewish-Moroccan family assigned to group C indicates that the ATC (A-T complementation group C) gene localizes to chromosome 11q22-q23 as well.

Diaphragmatic defects in children of consanguineous parents

Congeni ta l d iaphragmat ic defects have been classified by Bingham (1959) into posterolateral defects (foramina of Bochdalek) retrosternal defects ( foramina of Morgagni) , and the rare extensive defects involving most or all of the hemidiaphragm (agenesis). Famil ial occurrence of d iaphragmat ic hernia is rare and in most families in which this has been reported the pat ients have died from extensive defects within a few days of bir th (Daent l and Passarge, 1972). Daent l and Passarge summarized nine reported families in whom 20 of 29 siblings were affected with agenesis of the diaphragm. In view of the rari ty of d iaphragmat ic agenesis it was suggested that this lesion might be etiologically different f rom the other two types of the defect, which do not show increased familial incidence (Passarge et al., 1968). The role of genetic factors in the etiology of familial agenesis of the d iaphragm is unclear. Autosomal recessive and mult ifactorial inheri tance have been suggested (Passarge et al., 1968; ten Kate and Anders, 1970; Jensen and Altrogge, 1971; Daent l and Passarge, 1972). No parenta l consanguin i ty has been reported. In this report we present two affected sisters who are the offspring of a consanguineous marriage.

Pseudodeficiency of α-galactosidase A

Apparent deficiency of α‐galactosidase A was observed in a 51‐year‐old, clinically healthy male, with no clinical symptoms of Fabry disease, and without excess urinary excretion of ceramide trihexoside. The deficiency, which was similar to that found in Fabry disease patients, could be demonstrated using both synthetic and natural substrates. This pseudo‐deficiency was transmitted in his family by classical X‐linked inheritance. His wife showed enzyme activity in the normal range, two daughters were heterozygotes for this mutation as demonstrated by hair root assay, and three sons showed normal α‐galactosidase activity. Kinetic studies in cultured skin fibroblasts indicated a five‐fold increase in the apparent Km and a greater heat stability of the residual α‐galactosidase activity when compared to controls. These data indicate that the residual enzyme activity in this mutation behaves similarly to that observed in Fabry disease patients but does not cause any clinical abnormalities.

The femur, fibula, ulna (FFU) complex in siblings

Two siblings affected with the Femur, Fibula, Ulna (FFU) complex are reported. The FFU complex is relatively common, but was not previously reported in relatives.

Selective hypoaldosteronism in Iranian Jews: An autosomal recessive trait

A salt‐wasting syndrome associated with high plasma renin activity and inappropriately low aldosterone levels was observed among eight Jewish families from Iran. Aldosterone deficiency was due to an inborn error selectively involving the terminal portion of the biosynthetic pathway and characterized by an enzymic block in the conversion of 18‐hydroxycorticosterone to aldosterone. The analysis of the eight pedigrees, including 12 affected children, shows a high coefficient of inbreeding. Genetic analysis, by two independent methods, strongly suggests an autosomal recessive mode of transmission of the syndrome.

Genetics of insulin dependent diabetes mellitus in Israel: Population and family study

The association between insulin dependent diabetes mellitus (IDDM) and the HLA system was studied in two groups of Jewish patients: 50 Ashkenazim and 42 non-Ashkenazim. The pattern of association of HLA-A and B locus antigens was somewhat different from that observed in European Caucasian patients. HLA-B8 had a higher frequency; B15 and Cw3 were rare in the population studied and were less frequent in IDDM patients than in controls. On the other hand, the frequency of A26, B18, and Bw38 was increased in Ashkenazi patients, but not in non-Ashkenazim, who in turn showed an increase for Bw51. Although the association between IDDM and HLA-A and B locus antigens shows a marked variability in different populations, the association with HLA-DR3 and DR4 is constant feature. There was a typical excess of DR3/DR4 heterozygotes in both patient groups. This heterozygote type carries the highest relative risk, followed by DR4/DR4 homozygotes. These data can well be interpreted by a model of two different HLA-linked susceptibility genes, one associated with DR3 and the other one with DR4, that interact so that different genotypes are associated with different levels of penetrance. This model received further support from studies in 15 multiple case families where there is an excess of affected sib pairs sharing two DR antigens.

HLA-DR,D recombination in a kidney transplant recipient

Immunogenetic studies of a consanguineous family revealed discordance in the inheritance pattern of the HLA-D and HLA-DR antigens in one offspring. The findings suggest a recombination between the HLA-D and HLA-DR loci in one of the paternal chromosomes. Results on segregation of B-cell alloantigens. MLC reactivity, and glyoxalase isoenzyme determination map the DR gene between the HLA-B and D loci.