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Biomedical subjects

M Frydman

Publications and source records attributed to M Frydman.

At least 37 records · Page 2Linked to original sources
PubMed1990

A single origin of phenylketonuria in Yemenite Jews.

Phenylketonuria (PKU) is a metabolic disease caused by recessive mutations of the gene encoding the hepatic enzyme phenylalanine hydroxylase (PAH). The incidence of PKU varies widely across different geographic areas, and is highest (about 1 in 5,000 live births) in Ireland and western Scotland, and among Yemenite Jews. A limited number of point mutations account for most of the PKU cases in the European population. Here we report that a single molecular defect--a deletion spanning the third exon of the PAH gene--is responsible for all the PKU cases among the Yemenite Jews. Examination of a random sample of Yemenite Jews using a molecular probe that detects the carriers of this deletion indicated a high frequency of the defective gene in this community. Although the deleted PAH gene was traced to 25 different locations throughout Yemen, family histories and official documents of the Yemenite Jewish community showed that the common ancestor of all the carriers of this genetic defect lived in San'a, the capital of Yemen, before the eighteenth century.

Alleles↗
PubMed1990

Possible heterogeneity in spondyloenchondrodysplasia: quadriparesis, basal ganglia calcifications, and chondrocyte inclusions.

We report on 6 patients with short stature and progressive enchondromatous-like changes of the vertebral bodies and the metaphyses of the long bones. Parental consanguinity was observed in 5 of 6 cases, supporting autosomal recessive inheritance. In spite of the similarity in radiographic changes and body proportions, genetic heterogeneity is suggested by the presence of CNS calcifications in 3 patients. Two of the latter had progressive quadriparesis. We tentatively classified these patients into 2 provisional types. An iliac crest biopsy in one of the patients with "type I" disease did not demonstrate enchondromatosis. Light and transmission electron microscopic studies demonstrated large cisterns and small inclusion bodies containing a flocculent material within the rough endoplasmic reticulum of the chondrocytes. Based on the histological and radiographic findings, we propose to classify these conditions among the spondylometaphyseal skeletal dysplasias.

Adolescent↗
PubMed1990

Ambiguous genitalia in the Proteus syndrome.

An 11-year-old girl was followed up since birth because of hemihypertrophy of the left leg and thigh, multiple pigmented nevi and subcutaneous tumors typical of the Proteus syndrome. Because of clitoromegaly and scrotal-like hypertrophy of the labia majora, she had an endocrine evaluation the results of which were normal. The findings are thought to represent local genital hypertrophy. Ambiguous genitalia have to be added to the phenotype of the Proteus syndrome.

Abnormalities, Multiple↗
PubMed1990

Megalocornea, macrocephaly, mental and motor retardation (MMMM).

Two patients with macrocephaly, mild mental retardation and megalocornea are reported. Hypotonia, poor coordination and swallowing difficulties were present. One patient was obese and the other had scoliosis. Both had large fleshy ears and long fingers. The spectrum of the mental retardation megalocornea syndrome is not fully defined. These two patients resemble a previously reported case, and although there are distinct differences from patients with familial or sporadic Neuhauser syndrome, these cases may represent clinical variability of that syndrome.

Adolescent↗
PubMed1990

Wilson's disease in Israel: a genetic and epidemiological study.

Clinical and family history data on persons affected with Wilson disease (WD) living in Israel between 1958 and 1984 were ascertained from the literature, hospital records and neurological and gastroenterological clinics. From this population of 51 families, representing a diversity of Middle Eastern. North African and European backgrounds, blood samples were collected from affected individuals in 21 families, their parents, sibs and other relatives for quantitative determinations of plasma copper and ceruloplasmin, liver tests and DNA analysis. Although the majority of patients have the hepatic form of the disease, hepatic and neurological cases were found among all ethnic groups. In fact, affected sibs in several inbred families who most likely inherited two copies of the same mutant allele had different symptoms. Gene frequencies were calculated for each of the populations taking into account inbreeding, probability of ascertainment, and estimated incidence. Although many of these communities have gene frequencies which are comparable to worldwide estimates, high prevalence of disease is maintained by consanguineous mating patterns. Probabilities of WND genotypes were calculated for 129 unaffected relatives who had an a priori risk of inheriting at least one WND allele using information from 10 DNA markers closely linked to the WND locus. There was no evidence that multiple loci are responsible for the observed clinical variability in this sample of families. Furthermore, studies of serum copper and ceruloplasmin levels in unaffected relatives suggest that phenotypic variability in WD may be due in part to an interaction of the WND locus with other genetic or non-genetic modifiers such as age.

Adolescent↗
PubMed1990

Schizophrenia and Marfan syndrome.

Five index patients and three of their first-degree relatives were affected both by schizophrenia and Marfan syndrome. Since the association appears statistically significant, the possibility of linkage disequilibrium between adjacent genes or a cytogenetic abnormality causing both disorders is suggested. These hypotheses are testable and hold promise in attempting to map the 'schizophrenia susceptibility gene' by the candidate-gene approach.

Adult↗
PubMed1989

Interstitial deletion 2q14q21.

A girl with multiple congenital anomalies and a tendency to severe pyogenic infections was found to have an interstitial deletion of chromosome band 2q14----q21. Unusual facial manifestations included enophthalmos, long philtrum, micrognathia, narrow forehead, prominent glabella, and depressed nasal bridge. Unilateral corneal clouding, with Peters-like anomaly; agenesis of the corpus callosum; brain atrophy; and heart, kidney, hand, and dermatoglyphic anomalies were additional findings. Eye anomalies were observed in five of 22 patients with deletions of chromosome 2q. In comparing these cases, it seems that deletions of bands 2q21 and 2q31 are variably associated with microphthalmia, corneal clouding, cataracts, and Peters anomaly. Measurement of protein C and interleukin-1 (IL-1) did not show a gene dose effect, but the pyogenic infections and low IgA found in this patient may reflect an abnormality of IL-1 not detectable by our methods.

Abnormalities, Multiple↗
PubMed1989

G2 chromosomal radiosensitivity in families with ataxia-telangiectasia.

Ataxia-telangiectasia (A-T) is an autosomal recessive disease involving chromosomal instability, susceptibility to cancer and X-ray hypersensitivity. The latter two features are expressed to a limited extent in the heterozygous carriers of A-T mutations. Although fibroblast lines from A-T heterozygotes clearly show increased susceptibility to the lethal effect of X-irradiation, the difference in post-irradiation survival between cell lines and normal controls is not always large enough to allow the use of X-ray sensitivity as a laboratory assay for carrier detection in A-T. Recently, we have shown in a blind study, that the extent of chromatid damage induced in the G2 phase of the cell cycle by moderate doses of X-rays is markedly higher in A-T heterozygous cells than in normal controls. We have now applied this test to 6 additional obligatory heterozygotes and 24 individuals with different risks of being A-T carriers, from three Israeli A-T families. All 6 cell lines from the obligatory heterozygotes showed the typical hypersensitivity to the clastogenic action of X-rays in G2; of the 24 cell lines with unknown A-T genotype, 16 showed the same hypersensitivity, and 8 responded in a normal way. The proportion of cell lines showing the "A-T-heterozygous phenotype" was in accord with the expected value, based on Mendelian chance calculations. Since these observations were made, a daughter of two hypersensitive parents in one of these families has been diagnosed as having A-T. This confirmed the presumed A-T heterozygosity of the parents, as indicated by the laboratory assay.

Ataxia Telangiectasia↗
PubMed1989

Cardiac involvement in glycogen storage disease type III.

Twenty patients with enzymatically proven glycogen storage disease type III (GSD III) aged 3-30 years underwent cardiological evaluation. Seventeen showed subclinical evidence of cardiac involvement in form of ventricular hypertrophy on ECG. Of 16 patients in whom an ECG examination was performed, 13 had abnormal echocardiographic features. Only 2 patients had cardiomegaly on X-ray. The cardiac findings in 1 of the patients, a 25-year-old female with clinically evident cardiomyopathy are described in detail. In view of our findings, patients with established GSD III, should not only be investigated regarding their muscular involvement, but should also undergo a detailed evaluation of their cardiac status.

Adolescent↗
PubMed1989

Hypouricemia due to familial isolated renal tubular uricosuria. Evaluation with the combined pyrazinamide-probenecid test.

A Jewish Iraqi woman with familial isolated renal tubular uricosuria, urate clearance of 60.5 +/- 5.7 ml/min and hypouricemia of 1.0 +/- 0.2 mg/dl is described. The combined pyrazinamide-probenecid test suggested a presecretory defect in urate reabsorption. Four offspring were moderately affected. This family represents the sixth Jewish Iraqi family with familial isolated presecretory uricosuria, and emphasizes the marked prevalence of this disease among the Iraqi Jewish population. Since the inheritance of the presecretory defect is autosomal recessive, we suggest that this family is an example of pseudodominant transmission. The combined pyrazinamide-probenecid test may cause a reduction in glomerular filtration rate and filtered load of urate and thereby affect urinary excretion rate of urate in patients with urate wasting.

Creatinine↗
PubMed1988

Familial simple hypohidrosis with abnormal palmar dermal ridges.

A brother and sister born to nonconsanguineous, Iranian Jewish parents were found to have simple hypohidrosis. Pilocarpine produced only little sweating, and external heat and physical effort were associated with elevation of body temperature. Abnormal palmar dermal ridges were considered to be associated with paucity of sweat pores and glands. Biopsy supported this view since only one normal sweat gland and duct was found in a 5 mm punch.

Adolescent↗
PubMed1988

Predicting genotypes at loci for autosomal recessive disorders using linked genetic markers: application to Wilson's disease.

Recently, the Wilson's disease locus (WND) has been mapped to the long arm of chromosome 13. We have analyzed segregation of several chromosome 13 markers flanking the WND locus and used multipoint linkage analysis to determine the most likely WND genotype of each of 57 unaffected individuals in 5 Wilson's disease families. Approximately 46% of these could be classified as carrier (heterozygote), homozygous normal, or homozygous affected (not yet symptomatic) with a probability of at least 90%, while 77% could be classified with a probability of at least 80%. Our results demonstrate that even though there is a significant decrease on average in serum copper concentration in Wilson's disease heterozygotes compared to normal homozygotes, other sources of variation in serum copper concentration are much greater and preclude use of serum copper to detect heterozygotes for Wilson's disease. Subsequent analyses showed that a familial component, independent of WND genotype, is the major factor accounting for variation in ceruloplasmin levels among unaffected individuals; age is another factor accounting for more variation in copper levels among unaffected individuals than WND genotype.

Ceruloplasmin↗
PubMed1988

Linkage studies do not confirm the cytogenetic location of incontinentia pigmenti on Xp11.

Linkage studies have been performed in 5 incontinentia pigmenti (IP) families totaling 29 potentially informative meioses. Ten probes of the Xp arm were used, six of them were precisely localized on the X chromosome, using hamster X human somatic cell hybrids containing a broken X chromosome derived from an incontinentia pigmenti patient carrying an X;9 translocation [46,XX,t(X;9)(p11.21;q34)]. The following order for probes is proposed: pter - (DXS7, DXS146, DXS255) - IP1 - (DXS14, DXS90) - DXS106 - qter. The negative lod scores obtained exclude the possibility that in the families studied, the gene for IP is located in Xp11 or in the major part of the Xp arm.

Animals↗
PubMed1988

Single intramuscular dose of ceftriaxone as compared to 7-day amoxicillin therapy for acute otitis media in children. A double-blind clinical trial.

Fifty-two children (mean age 23 months) with acute otitis media were treated randomly with either a single intramuscular dose of ceftriaxone (Rocephin) 50 mg/kg (27 patients) or 7 days of amoxicillin 12.5 mg/kg t.i.d. (25 patients). The rate of resolution of acute symptoms and incidence of recurrences and relapses during the first months after commencement of the therapy was similar in the two groups. One week following the start of treatment no difference was observed in the proportion of patients with tympanometric evidence of middle ear effusion (MEE) in either of the two groups. On day 30, however, significantly more patients from the ceftriaxone group had flat tympanograms-83% as compared to 47% in the amoxicillin group. Therefore, single-dose ceftriaxone therapy cannot be suggested at present as routine therapy for acute otitis, although it may be considered a reasonable alternative in noncompliant patients.

Administration, Oral↗
PubMed1988

Eight closely linked loci place the Wilson disease locus within 13q14-q21.

Wilson disease (WD) is an autosomal recessive disorder resulting in an accumulation of copper in the liver, brain, and other organs. The WD locus (WND) has previously been linked to esterase D (ESD) and localized to 13q14-22. With the large Centre d'Etude Polymorphisme Humain cohort, a refined map of DNA markers from this region was constructed, with the following locus order: D13S1-D13S21-D13S22-D13S10-ESD-RB-WND-D 13S26-D13S12-D13S2. A significant excess of male recombination was observed between D13S21 and D13S22. Intervals distal to D13S22 showed an excess of female recombination. When these markers were tested on 19 WD families from a variety of ethnic backgrounds, the two closest loci were shown to be RB and D13S26. The retinoblastoma gene locus (RB) was shown to be proximal to WND at a distance of 4.4 centimorgans (cM), and D13S26 was placed distal to WND at a distance of 4.0 cM. ESD was assigned proximally at a distance of 9.4 cM. In all families studied WND was linked to one or more of the loci ESD, RB, or D13S26.

Chromosome Mapping↗
PubMed1987

Endocrine studies of the ovulatory disturbances in Wilson's disease (hepatolenticular degeneration).

Women with Wilson's disease may have severe oligomenorrhea or amenorrhea whose cause is unknown. The endocrine profile of four such cases was investigated by measuring basal values and the response to dynamic tests of hypothalamic, pituitary, thyroid, and adrenal function, which all proved normal. Ovarian function was disturbed, as witnessed by low estradiol, high total testosterone (T) levels with normal free T, and mildly elevated androstenedione. An interference of ovarian follicular aromatase activity possibly due to copper intoxication could explain these findings as the cause of the ovulatory disturbances of Wilson's disease.

Adolescent↗