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Peptidase A (PepA) activity was measured in five patients with trisomy or monosomy of the distal portion of 18q. The ratio propositus/mean parent (sum of the values of the father and mother divided by two) showed a gene dosage effect, confirming the localization of the gene in 18q23.

Full trisomy 7, without evidence of mosaicism, was observed in a newborn male having survived three months. Apart from facial dysmorphism, he had unusual malformations: severe anomalies of the splenomesenteric vascular system, persistence of Müllerian ducts (uterus masculinus), major anomalies of the anterior chamber of eye.

In two unrelated girls, each with severe mental deficiency and craniofacial dysmorphism, deletion of chromosome segment 1q4 had occurred de novo. These two observations together with seven others from the literature allow delineation of a syndrome, as follows. Growth retardation is marked at birth and remains beyond the 3rd percentile. Mental retardation is severe. Seizures are frequent. The cry may be unusually high pitched. Craniofacial dysmorphism includes brachymicrocephaly, a round and flat facies, a high forehead with a prominent metopic suture, thin and scarse hair, palpebral fissures slanted upward, hypertelorism and epicanthal folds, a bulbous nose with a flattened nose-bridge, a large and prominent philtrum, well-defined Cupid's bow, and retrognathia. Other malformations include various skeletal malformations, hypospadias with or without cryptorchidism, a consistent feature, and congenital heart disease in a third of the cases. The deletion occurred de novo in 8 out of the 9 cases. The breakpoint is, according to the several authors, in 1q42 or q43.

Two cases of del(13)-retinoblastoma are reported. Case 1, a 13-month-old male, was monosomic due to the malsegregation of the maternal ins(20;13)(p12;q1307q14.3). The patients's sister was trisomic for 13q1307q14.3 with no evident phenotypic effect. Case 2 was a 20-month-old female with a denovo del(13)(q1303q14.3). In both instances esterase D activity showed a remarkable gene-dosage effect in monosomy, disomy, and trisomy, thus confirming the assignment of the gene locus to 13q14, and more precisely to the proximal half of this band. In all instances, the ESTD phenotypes were 1-1. It is suggested that esterase D activity should become an important diagnostic criteria for the various etiological forms of retinoblastoma.

A female infant with a de novo del 6q14q16.2 and five other patients with del 6q1 reported in the literature allow the delineation of a characteristic syndrome, the main features of which are: severe mental retardation, a round face with full cheeks, upslanting palpebral fissures, a short neck, umbilical hernia, malpositioned feet with syndactyly II-III, and typical dermatoglyphics with an excess of whorls and clinodactyly of the Vth finger.

An orang-utan family is reported in which the father (Piku) is homozygous for a pericentric inversion of chromosome 3 and heterozygous for a structural rearrangement of chromosome 12 (author's nomenclature for this species). The latter is interpreted as transposition of the centromere by insertion into band q213 [ins cen(12)(q213)]. Piku's mate has a normal female chromosome complement. His daughters by this mate (Agnès and Ursula) are heterozygous for both his rearrangements. A fifth orang-utan (Arnold) captured on a different Malesian island was found to have one chromosome 12 similar to that of Piku, and to have a female complement, even though his keapers considered him male. Several hypotheses are proposed to explain the observations, including consanguinity, the existence of a common polymorphism in the species, and the existence of an established subspecies among orang-utans.

Mosaic trisomy 14 due to a de novo formation of an iso dicentric chromosome 14 was observed in a male negro infant who died at the age of one week. Together with three previous reports in the literature of mosaic trisomy 14, this observation allows the delineation of a syndrome characterized by intrauterine growth retardation ; craniofacial dysmorphism with frontal bossing ; hypertelorism ; microretrognathia, small, lowset, abnormally folded ears ; a translucent film over the eyes ; and congenital heart disease.

The phenotype of an 18-month-old male infant trisomic for the proximal portion of the long arm of chromosome 14 was reported and compared with that of previously reported cases. For the identification of the resulting syndrome, the most consistent features are psychomotor and growth retardation, and an oval, dysmorphic facies which includes a distinctive form of the mouth and a prominent nose. The trisomy in the child reported here is due to a familial translocation transmitted by the mother and present in at least three generations: t(12;14)(q24.4;q21). The 12q duplication in the child's genome is minimal and does not seem to have contributed to his phenotype.

The two probes H3-8 and H2-42, known to be located in 13q14, were mapped by in situ hybridization to either side of the 13 breakpoint of an apparently balanced de novo t(2;13)(p24.3;q14.2) detected in a patient with retinoblastoma as the only phenotypic manifestation.

The embryonic testicular regression syndrome associated with severe mental retardation is reported in three 46,XY sibs each of whom has a 46,XY chromosome complement. A fourth sib, a sister, also is severely retarded mentally; her chromosome complement is 46,XX. The 46,XY individuals, who were raised as females, presented varying degrees of genital ambiguity, indicating that their gonadal activities had been arrested at different times during embryogenesis. No trace of gonadal tissue could be found in either patient. The coincidence of the embryonic testicular regression syndrome and severe mental retardation in the same sibship is discussed.

The association of mental deficiency, macroorchidism, and a fragile site on chromosome X [fra (X)(q28) is reported in a 13-year-old boy who also exhibits a peculiar facies reminescent of trisomy 8. This particular facies is considered part of the clinical syndrome associated with the fra(X)(q28). The fra(X)(q28) was not found in the mother nor in two normal sibs of the propositus. The significance of the marker is discussed in view of two hypotheses, close linkage between pathological gene(s) and the fra(X)(q28) and faulty transcription of the gene(s) beyond the tra(X)(q28).

Three patients (two females, one male) are reported with bilateral aniridia, Wilms' tumor, more or less moderate mental retardation, decreased catalase activity, and del 11p13. These and 34 case reports from the literature are discussed with respect to: sex ratio, maternal age, type of chromosomal imbalance and frequency of associated rearrangements, prevalence of aniridia and other eye disorders, predisposition to tumor development, genitourinary anomalies, growth and mental retardation, and catalase involvement. Possible gene relationship within the complex locus and with neighbouring 11p genes is discussed.

Drash syndrome associates a nephropathy characterized by a diffuse mesangial sclerosis of early onset, Wilms tumor, and male pseudohermaphroditism (MPH). A patient with Drash syndrome is reported with the following: karyotype 46,XY, external genitalia near normal female, mixed gonadal dysgenesis, severe androgen receptor deficiency demonstrated for the first time in this syndrome. The possibility of a common genetic denominator with the del 11p13 WAGR complex is suggested. MPH/nephroblastoma association is common. Androgen receptor deficiency has been observed in one case of each syndrome, respectively.

Two unrelated patients with a strikingly similar phenotype (low birth weight and poor thriving; mental retardation; dolichocephaly; beaked nose; deeply set eyes; prominent maxilla and receding small chin; long fingers with a peculiar clench) were partially trisomic for two different segments of 9q. The segment found to be trisomic in both patients is small and corresponds to the q31q32 region. This new syndrome is compared to observations of trisomy 9 reported in the literature.

A familial t(X;2) (p223;q323) is responsible for partial trisomy 2q in the proposita, a 3-year-old girl with severe mental retardation and hypotrophia. It is present in the balanced state in the mother, two daughters, and one son. X-replication was studied after BUDR incroporation and acridine orange staining. The reproductive impairment of balanced X/autosome translocations is discussed.

A few cases of Beckwith-Wiedemann syndrome (BWS) have in common a duplication of 11p15. Among the genes located in 11p15, c-Ha-ras 1 (HRAS1), insulin (INS), and insulin-like growth factor II (IGF2) may account for the clinical features and the increased risk for malignancy. Using eight 11p15 markers including HRAS1, INS and IGF2 we have studied eight sporadic and hereditary cases of BWS whether or not associated with a nephroblastoma. By gene dosage determination and family studies, we have shown the following: the eight patients examined had an apparent diploid representation of all of the eight markers studied, thus indicating that a microduplication of these markers or of the region characterized by these markers is not a common event in BWS; in a family with three affected sibs the genes for HRAS1 and INS/IGF2 did not cosegregate with BWS and therefore may not participate in the pathogenic processes here observed.

Lymphocyte cultures from patients affected by retinoblastoma (Rb), with or without a microdeletion of chromosome 13, and Wilms tumor (WT), with a microdeletion of chromosome 11p where exposed to gamma-ray radiation during S and G2 phases. Chromatid and chromosome lesions were scored and compared to those observed in controls. No significant differences were detected, neither between patients and controls, nor between patients carrying or not a microdeletion. This lack of difference was unexpected since the genes for catalase and esterase D, also called S-formyl glutathione hydrolase, which are two detoxication enzymes, are deleted in case of microdeletion of 11p and 13q, respectively.

A patient with the phenotype of trisomy 21 (Down syndrome) was found to have a normal karyotype in blood lymphocytes and fibroblasts. Assessment of the chromosome 21 markers SOD1, CBS, ETS2, D21S11, and BCEI showed partial trisomy by duplication of a chromosome segment carrying the SOD1, CBS, and ETS2 loci and flanked by the BCEI and D21S11 loci, which are not duplicated. This submicroscopic duplication at the interface of 21q21 and 21q22.1 reduces to about 2000-3000 kb the critical segment the trisomy of which is responsible for the phenotype of trisomy 21.

The improvement of chromosome banding techniques has much increased the frequency of detected forms of retinoblastoma. Ten rearrangements involving 13q14 were observed in a series of 105 retinoblastoma patients including: five de novo deletions, one of them with suspected mosaicism; one de novo apparently balanced translocation; four deletions due to three familial insertions. Such a mechanism could account for pedigrees showing transmission of the tumor through unaffected carriers. Apparently unrelated rearrangements were also observed. Clinical aspects of these constitutional rearrangements are briefly discussed. Comparison with the literature data is presented.

Sister-chromatid exchanges were studied in fibroblasts from a child with del(13)-retinoblastoma. The skin biopsy was performed before the clinical onset of the tumor. The observed frequency of SCE, 19.65 per cell, was significantly increased as compared to that of a normal control, 14.68 per cell (t = 3.57, p < 0.001).

A satellited Y chromosome (Yqs) occurred de novo in a boy born to first cousins. The child had severe mental retardation, facial dysmorphism, congenital heart disease, and amaurosis, and died at 6 months and of age. The chromosome rearrangement was confirmed by R-, G-, C-, Q-, and Ag-NOR banding. Its significance and the difficulty of genetic counseling are discussed.

Hypomelanosis of Ito (incontinentia pigmenti achromians), a sacrococcygeal complex dysembryoma, seizures, severe cerebral lesions, mental retardation, chorioretinal atrophy, hemihypotrophy of the body, and skeletal anomalies are reported in a female infant of North African origin. Karyotype analysis revealed mosaicism for a microdeletion of the proximal region of 15q similar to that observed in Willi-Prader syndrome. The possibility of gene assignment of Ito's disease or that it may represent a nonspecific marker for mosaicism are discussed.

Sixty-six retinoblastoma patients were investigated using high resolution banding techniques, sister chromatid exchange (SCE) studies, and esterase-D phenotype determination and dosage. Seven patients (in six families) were found to be carriers of a rearrangement of band 13q14 due to de novo deletions, apparently balanced de novo translocations, or parental insertions. The possible role of submicroscopic parental insertions is suggested to explain transmission of nonchromosomal forms through unaffected carriers.

Renin, related to other aspartyl proteases, plays an important role in the cascade which regulates blood pressure and salt metabolism. A human renin 1 100 bp long cDNA including most of the coding region and the 3' non coding region has been subcloned by Soubrier et al., 1983. A 1000 b RNA probe derived by subcloning into pSP64 vector was hybridized to EcoRI and HindIII digests of the DNA of a panel of 24 man-rodent somatic cell hybrids. With HindIII, four restriction fragments were observed, two of them revealing polymorphism (8.4 kb and 6.0 kb). Analysis of the distribution of the human signal among the hybrids confirms the localization of the renin gene (REN) to human chromosome 1. The whole plasmid including the 1 100 bp long insert was used for regional mapping by in situ hybridization; 45% of silver grains were found on chromosome 1, with a clear peak at band 1q32 (33% of silver grains on chromosome 1) and a smaller one at band 1q42 (17%). These data favour a regional localization of the renin gene to 1q32-1q42. Mac Gill et al. (1987) have localized the REN gene to 1q25-1q32 using in situ hybridization. Thus, 1q32 could be the most probable localization. No other peak could be observed. This is in agreement with results obtained with somatic cell hybrids.