Interstitial deletions without phenotypic effect: prenatal diagnosis of a new family and brief review.

A 39-year-old woman (G4P1SAB2) was referred for amniocentesis for advanced maternal age. An interstitial deletion of the G-dark band 11p12 was found in the fetus. Blood from the mother and her previous son was cultured and the same deletion was found in both. The absence of phenotypic effect in this family further confirms that G-dark euchromatic deletions are compatible with a normal phenotype, and underlines the importance of checking familial karyotypes even when apparently unbalanced structural rearrangements are found at prenatal diagnosis.

Investigation of three patients with the "ring syndrome", including familial transmission of ring 5, and estimation of reproductive risks.

We report three cases of ring chromosome 5 [r(5)], two familial (mother and daughter) and one sporadic. The phenotype resembled that of the "ring syndrome" with prenatal onset of short stature, growth retardation, mild facial dysmorphism and normal psychomotor development. Extended metaphase and prometaphase chromosome preparations using G-, R- and Q-banding and scanning electron microscopy (SEM) failed to demonstrate deletion in the ring 5. Flow karyotype using the FACS cell sorter and peak area analysis showed the r(5) to be in the same position as the normal chromosome 5. The deletion that is presumably associated with ring formation appears to involve less that one megabase of DNA. In the "complex" rings, high resolution SEM showed fragile sites at the 5q34 and 5q35 region with frequent deletions at that site. A literature survey suggests that when a parent carries a ring chromosome about 80% of recognised pregnancies result in live birth. Of these, about half have a normal phenotype and karyotype, and half inherit the parental ring; about half of those acquiring the ring (20%) show significant mental retardation.

A further family with congenital renal proximal tubular dysgenesis.

A new syndrome of oligohydramnios, Potter's syndrome, and anuric renal failure leading to stillbirth or neonatal death from respiratory failure has recently been described. Histologically, there is renal tubular dysgenesis, especially of the proximal tubules, and apparent glomerular crowding. To date, five families have been reported, in four of which there have been affected sibs and in two parental consanguinity. The disorder is, therefore, thought to be inherited in an autosomal recessive manner.

The neurological complications of Anderson-Fabry disease (alpha-galactosidase A deficiency)--investigation of symptomatic and presymptomatic patients.

Anderson-Fabry disease is an X-linked inborn error of metabolism characterized by subnormal activity of the lysosomal hydrolase, alpha-galactosidase A. We have assessed the incidence and nature of neuropathy in 12 patients (seven affected men and five carrier females). Abnormalities of cutaneous thermal sensation were common, even in asymptomatic carriers, with a unique predilection for cold sensitivity which suggests involvement of small myelinated nerve fibres. Intracranial abnormalities were frequently detected by magnetic resonance imaging (MRI) in males, both with and without overt cerebrovascular disease, and were more extensive in older patients. Such abnormalities were not detected in carriers. Auditory and vestibular abnormalities were present in six patients, only one of whom was symptomatic. Cranial MRI and assessment of cutaneous thermal thresholds are sensitive techniques which can identify neurological involvement in asymptomatic patients. They may be of benefit in monitoring the effectiveness of enzyme replacement therapy and excluding the carrier state for the defective gene.

Ethical guidelines in fetal medicine.

The ethical guidelines in the clinical practice of fetal medicine are discussed, largely from the point of view of early prenatal diagnosis. The discussion concentrates on several specific aspects including counselling, good procedure, prenatal screening, disclosure of results including fetal sex, experimentation and assessment of new technologies and health education. The emphasis is placed on the importance of informed consent, choice and understanding on the part of the patient, and the professional competence of the doctor and other professionals she may meet.

First-trimester diagnosis of Lesch-Nyhan syndrome.

Chorionic villi were sampled at 8-9 weeks' gestation in four women whose fetuses were at risk for Lesch-Nyhan syndrome. Radiochemical assay of hypoxanthine phosphoribosyl transferase activity and fetal sexing (in two fetuses by means of a Y chromosome specific cDNA probe) showed that three fetuses were affected. The biochemical findings were confirmed after therapeutic abortion in two cases and spontaneous abortion in the third. Chorion biopsy and ultramicroscale enzymology may be a suitable alternative to recombinant-DNA-based methods for first-trimester diagnosis in selected diseases where the abnormal gene product is an enzyme expressed in the chorion by the 8th week of pregnancy.

Studies on human phenylalanine Mono-oxygenase. I. Restricted expression.

Enzyme assays for phenylalanine mono-oxygenase have been performed on a variety of non-hepatic human cell types under varying conditions. The cell types studied were cultured fibroblasts, short-term lymphocyte cultures, long-term lymphoblastoid cultures, cultured amniotic fluid cells, hair roots and placental extracts. The cultured cells were assayed after growth under standard conditions and in the presence of a high concentration of substrate, a low concentration of end-product, added hydrocortisone or dexamethasone and under combinations of these conditions. In no instance was a significant enzyme activity obtained.

Partial monosomy 7 with interstitial deletions in two infants with differing congenital abnormalities.

Two cases of interstitial deletion of chromosome 7 are presented, one involving the short arm and the other the long arm. The cytogenetic, dermatoglyphic, and clinical findings are compared with previously reported cases of chromosome 7 deletion. The patient with a short arm deletion differs clinically from the previously reported cases but, in common with a least one previous case, has a low total finger ridge count. His interstitial deletion involving the 7p13 leads to 7p21 region also differs from 7p deletions reported in earlier cases. The patient with a long arm deletion has an interstitial loss of the region between 7q11 and 7q21, corresponding to one of three groups of 7q deletion that have been recognised. The phenotypic changes in this group are less well defined than in the other two and the patient presented here differs clinically from the previously reported cases, apart from one phenotypically normal mosaic case, in lacking morphological abnormalities. He shares with one previous case both epilepsy and a high intensity of dermal ridge patterns.

Non-progressive cerebellar ataxia, aplasia of pupillary zone of iris, and mental subnormality (Gillespie's syndrome) affecting 3 members of a non-consanguineous family in 2 generations.

A family is reported in which a brother and sister both showed non-progressive cerebellar ataxia, aplasia of the pupillary zone of the iris, and mild mental subnormality. These clinical findings were similar to those in two previous case reports. Despite the birth of an affected son to the affected sister, this family is considered to confirm autosomal recessive inheritance of this syndrome. The paternity of the mother's husband is supported by blood groups and biochemical markers and it is presumed that the husband is a heterozygote, even though no consanguinity could be detected.

Brachydactyly and polydactyly with dermal ridge dissociation and ridge hypoplasia.

A child with brachymesophalangy and postaxial postminimal polydactyly was found also to have dermal ridge dissociation and ridge hypoplasia. She was the second child of unaffected, unrelated parents and was born after a normal pregnancy and delivery. No previous report of a similar combination has been traced.

Renal dysplasia and asplenia in two sibs.

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver. This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.

Inhibition of gill cilial activity and of Proteus vulgaris motility as tests for aspirin idiosyncrasy.

Aspirin ingestion is likely to result in severe asthmatic attacks in patients with aspirin idiosyncrasy. There is no in vitro test for the condition. Gill cilia and Proteus vulgaris motility studies showed no differences between asthmatics with aspirin idiosyncrasy and control patients.