“de novo” trisomy 1q32→1qter and monosomy 3p25→3pter

Summary The syndrome of familial lymphedema (type Meige) with distichiasis was observed in father and son. The association with uvula bifida and submucous cleft of the palate is described for the first time.     

Partial trisomy 13q21→qter de novo due to a recombinant chromosome rec(13)dup q

Summary A female is described who has a karyotype with an additional distal half of 13q in a recombinant rec(13)dup q chromosome. Since her parents have normal karyotypes, the origin of her karyotype is assumed to be a premeiotic pericentric inversion de novo with crossing-over within the inversion loop at meiosis. By means of various banding techniques, the breaks preceding the rearrangement could be located exactly. The joint between the duplicated segment and the satellites of the receptor chromosome is of special note. The phenotype of the patient stated at the age of 9 months and at the age of 71/2 years was found to be related to the segments involved in the partial trisomy. The clinical features were largely in accordance with previous case reports having an identical extent of the triplicated 13q segment.     

A case of trisomy 3q21→qter syndrome

Summary An infant with karyotype 46,XY,der(8),t(3;8)(q21;p23) is presented. The presence of trisomy 3q21qter syndrome is suspected on the basis of comparison of the clinical and laboratory findings of this patient with those of cases that have been reported as partial 3q trisomy. The common phenotypic features of this syndrome include growth failure and mental or developmental retardation, hypotonia, persistent lanugo, distorted head, congenital glaucoma, short and upturned nose, prominent maxilla, micrognathia, short, webbed neck, short limbs, retroflexed third and fourth toes, cutaneous syndactyly of the second, third and fourth toes, and elevated galactose-1-phosphate uridyl transferase activity in the red blood cells.     

Possible trisomy 1q25→1q32 in a malformed girl with a de novo insertion in 1q

Summary A newborn female is described who exhibited a characteristic facial dysmorphology including deep-set eyes, broad nasal bridge, small mouth, higharched and narrow palate, severely receding mandible and misshapen ears; constant flexion of the proximal interphalangeal joints, and short distal phalanges and nails of fingers; a congenital heart defect; marked muscular hypotonia, motor and growth retardation. She died at 4 months of age. Her karyotype revealed an additional band in 1q. Banding patterns and clinical picture suggest duplication of the segment 1q251q32.     

Assignment of the sorbitol dehydrogenase locus to human chromosome 15 pter→q21

The locus for sorbitol dehydrogenase (SORD, E.C. 1.1.1.14) has been shown to segregate with hexosaminidase A and mannose phosphate isomerase in a series of human-Chinese hamster somatic cell hybrids. Cytogenetic analysis supports the assignment to chromosome 15 and further defines the gene locus to the region 15pterq21.This research was supported by the Medical Research Council of Canada (MT 4061), the Children's Hospital of Winnipeg Research Foundation, Inc., and the Department of Health, Province of Manitoba (H.S.W.).     

Chromosome 7 short arm deletion, 7p21→pter

Summary A case report of a de novo deletion in the short arm of chromosome 7 is presented (46,XX,del(7)(p21pter)). The five-month-old girl's major symptoms are: trigonocephalus with craniosynostosis, median bony forehead bulge, high palate, atrial septal defect, anal atresia and perineal fistula, thumb insertion far to ulnar-proximal, and a slightly retarded psychomotor development. The other cases with monosomy 7p described in the literature are reviewed.     

Partial trisomy of the short arm of chromosome 3 (3p25→3pter)

Summary Two profoundly mentally mentally retarded brothers with partial trisomy for the distal part of the short arm of chromosome 3 (3p253pter) are described. Their anomaly arose as a segregation product of a balanced t(3p-;18q+) translocation in the mother. Compared with the other cases of partial 3p trisomy reported up to now, the present patients display a similar craniofacial dysmorphism with hypertelorism, broad nasal tip, short upper lip with prominent philtrum, and a large mouth with down-turned corners. Other stigmata, such as a prominent, high forehead with frontal bossing and full cheeks, were present during childhood but progressively disappeared.     

Moderate Down's syndrome in three siblings having partial trisomy 21q22.2→qter and therefore no SOD-1 excess

Summary Three mentally retarded siblings with moderate stigmata of Down's syndrome were found to have a partial trisomy 21q22.2qter resulting from a maternal translocation t(4q+;21q-). By the exclusion of any excess of SOD-1 in them, we can confirm the nonessentiality of the sub-band 21q22.1 and of the SOD-1 excess for most of the Down's syndrome stigmata including the mental retardation. However, the sub-band 21q22.1 in triplicate might be required for the completion of the full syndrome, as for example is shown by the incomplete dermatoglyphic pattern on the palms in the patients.     

Bisatellited dicentric chromosome: A report on a case with karyotype 47,XY,+psu dic(22)t(22;22)(22pter→cen→22q11::22q11→22pter)

Summary A 12-year-old boy with mental retardation and congenital anomalies was found to have a supernumerary small marker chromosome. This marker chromosome was proved to be bisatellited and dicentric by G-, C-, R-banding and the silverstaining technique.     

Interstitial deletion of the long arm of chromosome 7 46,XX,del(7)(pter→q2200::q3200→qter)

Summary We present a boy with the karyotype 46,XY,r3 and a phenotype with psychomotor and growth retardation, craniofacial anomalies, syndactyly of the toes, and edema of the feet. The karyotypes and phenotypes of both parents are normal.     

A point mutation,R59G,within the HMG-SRY box in a female 45,X/46,X,psu dic(Y)(pter→q11::q11→pter)

We report a molecular and cytogenetic investigation of a psu dic(Yp) chromosome identified in blood and ovarian tissue from a female with mosaic karyotype 45,X/46,X,+ psu dic(Yp). FISH analysis showed that the psu dic(Yp) has two copies of the short arm, two centromeres and two copies of the proximal long arm. PCR analysis also confirmed the presence of the SRY gene and the Y centromere, and also confirmed the deletion of the Y-heterochromatic region. Because of the possibility of a mutation, a fragment of 609 bp of the SRY gene was sequenced from independent PCR products. The analysis of the sequence indicated the presence of two different copies of the gene: one presented a point mutation, R59G, within the HMG-box; the other had a sequence identical to that already published. Both sequences were found at a proportion of 1:1. The absence of a 46,XY cell line suggests that the rearrangement took place during gametogenesis or during the first division after fertilization. Also, the existence of different sequences of the SRYgene in the same Y chromosome suggests that the formation of the dicentric took place prior to the mutation of the SRY gene. To our knowledge, this is the first time that a mutation has been described in codon 59 within the HMG- SRY box, and also the first case of a psu dic(Yp) chromosome that displays two different copies of the SRY gene.     

Pure monosomy and trisomy 2q24.2→q3105 due to an inv ins(7;2)(q21.2;q3105q24.2) segregating in four generations

Summary An inv ins(7;2)(q21.2;q3105q24.2) was found to segregate through four generations of a family. Adjacent-1 segregation aneusomies were ascertained in five patients: three monosomics and two trisomics; and the corresponding syndromes were delineated. The comparative analysis between these and other previously described 2q aneusomic individuals led to the conclusion that a large cleft between first and second toes is a constant feature in monosomy 2q24q31. No other trait could plausible be mapped. Risks of 7.9 to 31.9% for aneusomic children and of 26.3% for abortion were estimated in the present family.     

A boy with 47,X,del(X)(p11→q13::q21→q24),del(Y)(q11)

Summary A patient is described carrying a duplication 4p12pter due to a paternal translocation: 46,XY,t(4;16) (p12;p13). Involvement of chromosome No. 16 and the heterogeneity of the clinical picture in cases with dup (4p) are discussed.Postdoctoral fellow of the Deutsche Forschungsgemeinschaft.     

A newborn child with karyotype 47,XX,+der(12) (12pter→12q12::8q24→8qter),t(8;12) (q24;q12) pat

Summary A case of Meckel or Gruber syndrome is reported, together with a survey of the relevant literature of recent years (1971–1977), in reference to a probably autosomal recessive inheritance of this malformation.     

Partial trisomy of distal 8q derived from mother with mosaic 8q23.3→24.13 deletion,and relatively mild expression of trichorhinophalangeal syndrome I

Summary A 17-month-old girl with a partial trisomy of distal 8q derived from her mother, who has a mosaic 8q23.3q24.13 deletion, was studied. Both showed a relatively mild phenotype of trichorhinophalangeal syndrome I. The karyotype of the proposita was designated as: 46,XX,-8,+der(8),inv ins(8;8)(p23.1;q24.13q23.3)mat. Her phenotype was considered similar to that of her mother despite the trisomies of distal 8q. She seems to be the first example of a partial trisomy of distal 8q derived from a parent with an interstitial deletion of a distal 8q segment and trichorhinophalangeal syndrome I.     

Consequences of trisomy syndromes – 21 and beyond

The mechanisms underlying pathologies in Down syndrome remain poorly understood. In this forum article we compare the cellular phenotypes of chromosome 21 trisomy with other trisomic cells. We argue that both effects of the extra chromosome 21 and the global consequences of chromosome gain must be considered to understand complex pathologies of Down syndrome.     

Inherited and de novo deletion of the tyrosine aminotransferase gene locus at 16q22.1 → q22.3 in a patient with tyrosinemia type II

Summary Tyrosinemia II is an autosomal-recessively inherited condition caused by deficiency in the liver-specific enzyme tyrosine aminotransferase (TAT; EC 2.6.1.5). We have restudied a patient with typical symptoms of tyrosinemia II who in addition suffers from multiple congenital anomalies including severe mental retardation. Southern blot analysis using a human TAT cDNA probe revealed a complete deletion of both TAT alleles in the patient. Molecular and cytogenetic analysis of the patient and his family showed one deletion to be maternally inherited, extending over at least 27 kb and including the complete TAT structural gene, whereas loss of the second TAT allele results from a small de novo interstitial deletion, del 16 (pterq22.1::q22.3qter), in the paternally inherited chromosome 16. Three additional loci previously assigned to 16q22 were studied in our patient: haptoglobin (HP), lecithin: cholesterol acyltransferase (LCAT), and the metallothionein gene cluster MT1, MT2. Of these three markers, only the HP locus was found to be codeleted with the TAT locus on the del(16) chromosome.     

Serial duplication of 10 (q21→q22) in a mentally retarded boy with congenital malformations

Summary A boy with congenital malformations and a serial duplication of 10(q21q22) is reported. His clinical picture is compared with that of a previously reported patient with a similar karyotype.     

Women heterozygous for deficiency of the (p21 → pter) region of the X chromosome are fertile

Summary A woman balanced carrier of a X/15 translocation gave birth to a balanced infertile son and three unbalanced Xp- fertile daughters. This family and the other eleven cases of Xp- fertile women found in the literature demonstrate that loss of the p21 pter region of the X chromosome is compatible with fertility, probably because it leaves on Xp the region which is never inactivated.