Ichiro Murano

Fibroblast-specific common fragile sites induced by aphidicolin

SummaryThe distribution and frequency of aphidicolin-induced common fragile sites were studied in chromosomes of cultured skin fibroblasts and PHA-stimulated lymphocytes from five normal individuals; 0.2 μM aphidicolin was added for the last 26 h of culture. Skin fibroblasts from five fra(X)-positive patients were also studied in the same manner. Fragile sites most frequently found in fibroblasts from normal individuals were 3q26.2, 7q11.23, 16q23, 1p31, 10q11.2, 12q23 and 7q31, whereas those in lymphocytes from the same individuals were 3p14, 16q23, Xp22, 7q32 and 14q24. The distribution of fragile sites in fibroblasts from fra(X)-positive patients was essentially identical with that in normal individuals. The average number of gaps and breaks in 100 metaphases was 36.8 in fibroblasts from normal individuals, 113.8 in those from fra(X)-positive patients, and 279 in lymphocytes from normal individuals. Their rates of chromosome-type breaks and gaps were 7.9%, 29.7% and 54.5%, respectively. Thus, the distribution and frequency of aphidicolin-induced fragile sites were different between skin fibroblasts and lymphocytes, possibly reflecting differences in their DNA replication sequence or gene activity.

Cell type-dependent difference in the distribution and frequency of aphidicolin-induced fragile sites: T and B lymphocytes and bone marrow cells.

SummaryThe distribution and frequency of aphidicolin-induced common fragile sites were studied in Epstein-Barr virus-transformed B lymphocytes from eight normal individuals, and in bone marrow cells from six children in remission from malignant blood diseases. PHA-stimulated helper T lymphocytes from the same individuals were also studied. These cells were cultured in MEM, and treated with 0.2μM aphidicolin for 26 h. The results, together with those of our previous study on cultured skin fibroblasts, indicated that the distribution and frequency of aphidicolin-induced fragile sites are different among different types of cells.

Giant hepatic granuloma caused by Bartonella henselae.

We report a 10-year-old girl with a 3.0- by 3.5-cm giant hepatic granuloma caused by Bartonella henselae. Such a solitary and large granuloma associated with B. henselae infection has not been previously reported. We believe that B. henselae infection is a consideration in the differential diagnosis of a large hepatic mass.

Inverted insertion (9)(q34.3q22.3q21.2) and its recombination product: Duplication 9q21.2q22.3

To the Editor: We read with interest a recent article in your journal by Dr. Narahara and his colleagues (1986) who described a kindred with two carriers of what they interpreted as an intrachromosomal direct shift, dir ins(9)(q34.3q22.1q31.3), and a now 9-yearold girl with a recombinant chromosome 9. It was deduced that the rec(9) in the girl resulted from crossing over at one of two loops formed during meiosis I in her carrier mother, and thus carried duplication of the 9q22.1---~q31.3 segment. The ABO locus was assigned to 9q31.3-~ qter in view of the fact that the girl was a recombinant for the locus. We studied another kindred in which an apparently identical ins(9) chromosome is segregating through five generations. Our kindred and the maternal grandfather of the proband in Naraharas kindred both live in Tokuyama, a city with a 113,000 population. It is thus likely, but yet to be proven, that the two kindreds are related with each other. Our interpretation of the ins(9) is different from Naraharas (Fig. l, upper row). It involves insertion of an inverted 9@1.2,q22.3 segment into 9q34.3. Pairing of the inv ins(9) chromosome with a normal chromosome 9 during meiosis I in a carrier individual would produce two loops, one involving the inverted q21.2--~ q22.3 segment and the other the @2.3--+q34.3 segment (Fig. l, lower row). Odd numbers of crossing over in the latter loop would produce a recombinant chromosome with duplication of the q21.2--, q22.3 segment and one with deficiency of the same segment (Fig. 2). Family studies in our kindred disclosed three ins(9) carriers and two individuals with dup 9q21.2--,q22.3 (Fig. 3). It was deduced that both l 1-2 and 11-3, and also either I-i or I-2, were carriers of the inv ins(9) chromosome. Thus, the trait was transmitted through at least five generations. V-4, the proband in our kindred, a 2 year 2 month-old girl with dup 9q21.2 ~-, q22.3, weighed 1,874 g at birth. She walked at 15 months but did not speak meaningful words at age 2 2/12 years. She measured 76.6 cm ( 3 . 2 SD) and weighed 8 kg ( 3 SD). She had ocular hypertelorism, a short nose with a depressed nasal tip, short neck, low-set, malformed ears, fifth finger clinodactyly, absence of bilateral palmar triradii C and distally placed axial triradii. Her bone age was correspondent to her chronological age. III-5, a maternal distant relative of the proband, also carries the dup(q) chromosome. She is now 45 years old and mentally retarded, but no other details are known to us. The proband in Naraharas kindred, a 5year-old girl with dup 9q, had a low birth weight, growth deficiency, ocular hypertelorism, and dermatoglyphic abnormalities. Her IQ was 92 and her bone age

Interstitial deletion of 8p: report of two patients and review of the literature

Two female infants with de novo interstitial deletions of 8p were studied. One with a deletion from p11.21 to p11.23, and the other patient with a deletion from p11.23 to p21.3 had several clinical manifestations of the terminal 8p— syndrome. Band 8p11.23 was deleted in both patients. The clinical manifestations common to both patients included low birth‐weight, growth deficiency, congenital heart disease, mental retardation, dolichocephaly, low‐set, malformed ears, high‐arched palate, thin lips and micrognathia. Since these features may occur in most patients with chromosomal imbalance, and the terminal 8p— syndrome has hitherto been assumed to result from terminal deletions of 8p, ranging from p21.3 to p23, it is likely that these features are simply related to the chromosomal imbalance rather than to band specific imbalance of 8p11.23. The present study suggests that two different types of deletion, interstitial and terminal, are associated with still poorly defined, rather non‐specific clinical features.

Pigmentary dysplasias in long survivors with mosaic trisomy 18 : report of two cases

We describe two patients, a 19‐year‐old girl and a 19‐year‐old boy, with mosaic trisomy 18 and pigmentary dysplasias. Both patients had profound growth and mental retardation, marked kyphoscoliosis, bushy eyebrows, bulbous nose, simple ears, and joint contractures ‐ clinical manifestations of long survivors with mosaic or non‐mosaic trisomy 18. In addition, the boy showed total asymmetry. Pigmentary dysplasias of the skin with hypopigmented whorls and streaks, initially absent or overlooked at the ages 2 and 15 years, were detected on close examination. It is advisable to check closely every long survivor with mosaic or purportedly non‐mosaic trisomy 18 for pigmentary dysplasias.

Cell type-dependent difference in the distribution and frequency of excess thymidine-induced common fragile sites: T lymphocytes and skin fibroblasts

SummaryCommon fragile sites were induced by excess thymidine in phytohemagglutin-stimulated T lymphocytes from 4 normal individuals, and skin fibroblasts from 4 normal and 5 fra(X) positive individuals. The results indicate that the frequency and distribution of excess thymidine-induced fragile sites are different between these two types of cells. The sites at 1p13 and 2p11.2, induced in both types of cells, have not previously been described, and are thus considered to be excess thymidine-specific fragile sites. These findings extend and support our previous studies on cell type-dependent difference in aphidicolin-induced common fragile sites.

Common fragile sites induced by folate deprivation, BrdU and aphidicolin: their frequency and distribution in Japanese individuals.

SummaryThe frequencies and distribution of common fragile sites in normal Japanese individuals were studied using lymphocyte chromosome preparations from cultures under folate deprivation, 5-bromodeoxyuridine (BrdU) or aphidicolin treatment. Defining the 4% level of total breaks as a cut-off point, 13 folate-sensitive, 20 BrdU-induced and 8 aphidicolin-induced sites were identified in one or more individuals studied. After eliminating overlapping, 28 fragile sites were identified. Of these, 23 have been reported, while the other five have not been described. Of the latter, those at 4q34 and 6q22 were each found in only one individual. The site at 3q26.2 has not been reported but one at 3q27 has been identified. Excluding these three sites as inconclusive, there remain two sites hitherto undescribed: 1) a folate-sensitive site at 17q21, found in two of eight individuals studied, and 2) a BrdU-requiring site at 13q31, found in five of eight individuals.

A 7q-son of an XYY father

SummaryA 47,XYY man had a son with deletion of the distal segment of 7q and a karyotypically normal daughter.

Chronic Nephritis, Sensorineural Deafness, Growth and Developmental Retardation, Hyperkinesis, and Cleft Soft Palate in a 5-Year-Old Boy

A 5-year-old Japanese boy showed nephritis similar to, but distinct from, that in Alport syndrome. Nephrotic syndrome without hematuria was noticed at age 2, although renal biopsy at age 4 revealed widespread irregular thickening of the glomerular basement membrane with splitting of the lamina densa on electron microscopy, characteristic of nephritis in Alport syndrome. Sensorineural deafness was noticed at age 4 weeks by no auditory brain stem response, unusually early for Alport syndrome. Goodpasture antigen and amyloid P component were found in the glomerular basement membrane. Thus, the antigenicity of the glomerular basement membrane was different from that in male patients with X-linked Alport syndrome. In addition, growth and developmental retardation, hyperkinesis, and cleft soft palate were seen. These features are a hitherto undescribed combination. The family history was negative for any of the features of the boy.