Partial trisomy 2q and familial translocation t(2;12)(q31;q24)

Summary Report is given of a boy with trisomy of the distal part of the long arm of chromosome 2 (q31ter) due to a balanced 2/12 translocation in the mother: 46,XX,t(2;12) (q31;q24). Other phenotypically normal carriers of this balanced translocation are the patients sister and grandfather. The patient shows a variety of dysplastic signs mainly of the face.     

2 cases of partial trisomy 10p due to a paternal translocation t(10p;18)(p13;q23)]

Two brothers trisomic for the distal two thirds of 10p are reported. Trisomy results from the malsegregation of a familial translocation rcp (10;18)(p13;q23) present in the father, a half-brother and the grand-father of the propositi. The phenotype is comparable to that of other 10p trisomic patients reported in the literature.     

Neuropsychiatry and deletions of 18q; case report and diagnostic considerations

The 18q deletion syndrome can be caused by several terminal and interstitial deletions of which terminal deletions of the distal part of 18q are the most frequent and known as the DeCroughy syndrome. The neuropsychiatric phenotype is not well documented and includes disorganised and disinhibited behaviours as well as language difficulties. Non development of language seems to be specific for cases with a more proximally located interstitial deletions. In the present paper a 18-year-old severely mentally retarded male with an interstitial deletion of 18q is described (46.XY,del(18)(q12.1q22.1) who was referred for behavioural problems and neuropsychiatric evaluation. No categorical psychiatric diagnosis could be established. Given this and other reports, it is advocated to describe the psychopathological phenotype of 18q deletions in a dimensional way that will result in a clinical picture characterised mainly by symptoms from the motor and motivation domains. Treatment should include primarily behavioural measures, combined if necessary with symptomatic psychopharmacotherapy.     

Mosaic and non-mosaic trisomy 15q2

Two unrelated patients are presented. In the first mosaicism with normal cells and cells trisomic for the distal long arm (q2) of chromosome 15 was found. The 15q2 trisomy was due to a chromosome 14, to the long arm of which an extra 15q2 region was attached (14pter----14q32::15q22----15qter). In the second trisomy 15q2 was present as a consequence of a balanced t(7;15)(p22;q15) translocation in the mother.     

Partial trisomy 11q syndrome (11q23.1-->11qter) due to de novo t (11q; 13q) detected by multicolor fluorescence in situ hybridisation

In this report we describe the identification of a de novo 46, XX, 13q + by multicolour fluorescence in situ hybridisation (M-FISH), as a partial distal 11q trisomy (11q23.1-->11qter). The clinical phenotype association with this distal 11q trisomy is briefly reviewed.     

De novo translocation (2;18)(q21;q22) in a child with severe epilepsy, developmental delay and mild dysmorphism

De novo translocation (2;18)(q21;q22) in a patient with severe epilepsy developmental delay and mild dysmorphism: We report on a patient presenting with severe epilepsy, hypotonia, developmental delay, blepharophimosis, low-set ears, camptodactyly and tapering fingers, and cutaneous syndactyly of toes II and III of the right foot. The MRI showed some loss of volume of the white matter and delayed myelination, no other specific anomalies were present. Chromosome analysis revealed a translocation involving chromosomes 2 and 18, which was characterized further by FISH using band-specific probes. The possibility of a submicroscopic deletion is discussed and the patient is compared with patients reported in the literature with either 2q21 or 18q22 deletion.     

19q distal trisomy due to a de novo (19;22)(q13.2;p11) translocation

A 2 4/12-year-old girl whith a de novo 46,XX,-22 + der(22), t(19;22)(q13.2;p11) karyotype is described. From this and other eight similar cases previously published, a typical phenotype in distal 19q trisomy is concluded.     

Linkage of hereditary distal myopathy with desmin accumulation to 2q

We are investigating the genetics of a large family with an autosomal dominant form of hereditary distal myopathy. This slowly progressive myopathy begins during early adulthood in the distal leg muscles, producing a gait disturbance. Cardiomyopathy is also present in most affected family members, manifesting itself as conduction block or congestive heart failure. Histologically, an accumulation of the protein, desmin, occurs in the subsarcolemmal spaces of myofibers. We have performed linkage analyses of this family, and have mapped the location of the gene causing the myopathy to human chromosome 2q33. The gene is within a 17-cM segment of chromosome 2q bounded by the DNA markers D2S2248 and D2S401. The best candidate gene for this myopathy is desmin.     

Recombination events that locate myotonic dystrophy distal to APOC2 on 19q

We previously reported a recombination in an individual with myotonic dystrophy (DM) which placed the markers D19S19 and APOC2 on the same side of the DM locus. Haplotyping of this family with more recently characterized probes which are either tightly linked to DM or distal to the linkage group at q13.2 shows that the DM locus is distal to APOC2. This is confirmed by other recombinants where DM segregates with distal probes. Additional marker to marker recombinations in unaffected individuals are reported and support the order and orientation of the DM linkage group as pter-(INSR, LDLR,S9)-(S19,BCL3,APOC2)-(CKMM,DM)-(S22,+ ++PRKCG)-qter. The data presented here cannot determine whether DM is proximal or distal to CKMM. The consequences of this probe order for antenatal diagnosis and future research aiming to isolate the gene which is affected in DM are discussed.     

18q deletion syndrome in a child with steroid-17,20-lyase deficiency

The del (18q) syndrome is characterised by poor growth, variable mental retardation, facial dysmorphism, and abnormalities of the genitalia. In genetic males, genital abnormalities vary from testicular ectopia, and microphallus to severe hypospadias. Genetic females frequently have hypoplasia of the labia minora. We describe a child with del (18q) syndrome and severe ambiguous genitalia. Serum testosterone after 4 doses of hCG (5000 IU/m2/dose) was only 50 ng/dL (expected greater than 300 ng/dL). When testicular tissue was incubated with [1,2-3H]progesterone and 17-hydroxy-[4-14C]progesterone, there was synthesis of 17-hydroxy-[1,2-3H]progesterone but no further metabolism of 17-hydroxyprogesterone to androgens. These data suggested the presence of steroid-17,20-lyase deficiency. In order to determine if steroid-17,20-lyase deficiency was a common feature in del (18q) syndrome we examined 6 other patients (3 girls; 3 boys) with a deletion of the long arm of chromosome 18 distal to band q21. All 6 had dehydroepiandrosterone sulfate (DHEA-S) levels which were lower than those of age-matched controls. Four had delayed puberty. Serum testosterone levels were also low in 2 of the 3 affected boys. These results together with the findings in the index case suggest that a structural or regulatory gene for steroid-17,20-lyase may be located on the long arm of chromosome 18, distal to band q21.     

A large family with subtelomeric translocation t(18;21)(q23;q22.1) and molecular breakpoint in the Down syndrome critical region

We describe a 17-month-old infant with clinical features of Down syndrome and a normal karyotype by standard chromosomal analysis, her two uncles aged 28 and 30 years, respectively, with reduced intelligence and unusual appearance but not apparent Down syndrome, and a severely retarded 6-year-old girl with dysmorphy and epilepsy from the same family. Cytogenetic studies of patients and normal intervening relatives had been carried out at different institutions with normal results. Fluorescence in situ hybridization using whole chromosome painting and unique-copy probes (cosmids) and high-resolution banding revealed a familial subtelomeric translocation of chromosomes 18 and 21, resulting in partial trisomy 21 in the infant and her two uncles, and partial monosomy 21 in the 6-year-old girl. Cytogenetic breakpoints were located in bands 18q23 and 21q22.1, respectively. The molecular breakpoint on chromosome 21 was located between D21S211 (proximal) and D21S1283 (distal) and thus maps within the Down syndrome critical region. Received: 11 November 1996 / Accepted: 29 April 1997     

Paroxysmal dystonic choreoathetosis: tight linkage to chromosome 2q.

Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary movements that last up to several hours and occur at rest both spontaneously and following caffeine or alcohol consumption. We analyzed a Polish-American kindred with autosomal dominant PDC and identified tight linkage between the disorder and microsatellite markers on chromosome 2q (maximum two-point LOD score 4.77; recombination fraction 0). Our results clearly establish the existence of a locus for autosomal dominant PDC on distal chromosome 2q. The fact that three other paroxysmal neurological disorders (periodic ataxia with myokymia and hypo- and hyperkalemic periodic paralysis) are due to mutation in ion-channel genes raises the possibility that PDC is also due to an ion-channel gene mutation. It is noteworthy that a cluster of sodium-channel genes is located on distal chromosome 2q, near the PDC locus. Identifying the PDC locus on chromosome 2q will facilitate discovery of the PDC gene and enable investigators to determine whether PDC is genetically homogeneous and whether other paroxysmal movement disorders are also genetically linked to the PDC locus.     

Distal duplication 14q: Report of three cases and further delineation of the syndrome

Summary Three cases of distal duplication 14q are presented. The first two cases are cousins in a kindred segregating a balanced translocation t(14;18)(q31;q23). The third case resulted from a maternal translocation t(14;18)(q24;p11). By review of these cases and those previously reported, a distal duplication 14q syndrome is further delineated. Common features include postnatal growth retardation, mental retardation, hypotonia, microcephaly, slanted palpebral fissures, ocular hypertelorism, sparse eyelashes and eyebrows, nasal dysmorphism, tented lip, micrognathia, posteriorly rotated ears, and minor skeletal anomalies.     

Mosaic isodicentric chromosome 18q: sixth report and review

We describe a girl with a mosaic isodicentric chromosome 18q with discrete features of trisomy 18. She presented with prenatal growth retardation, prominent occiput, small face, high nasal bridge, large nose, thin lips, a perimembranous ventricular septal defect, and subsequent slow psychomotor development and slow growth. Amosaic isopseudodicentric chromosome 18q was detected in cultured lymphocytes: mos 46,XX,psu idic(18)(q23)[74]/ 46,XX[26]. Monosomy of the distal end of 18q23 could not be confirmed by fluorescent in situ hybridization (FISH) with RP 1l-565D23, one of the most telomere located probes of 18q23. Isopseudodicentric chromosome 18q is very rare. Most cases are mosaics. The phenotype varies. More or less distinct features of trisomy 18 and monosomy 18q can be found depending on the degree of mosaicism and the breakpoint in 18q.     

Partial trisomy 8q and partial monosomy 18p: a case report

We report clinical observations and cytogenetic studies of an inherited partial trisomy 8q and partial monosomy 18p. A full trisomy 8 syndrome (Warkany syndrome) is a clinically recognized syndrome. Partial trisomy 8q has been reported sporadically in the literature with variable phenotypes. Partial monosomy 18p, deletion of the short arm of chromosome 18, is also a well-recognized syndrome. This is the first report to the best of our knowledge of partial trisomy for distal 8q and partial monosomy for distal 18p occurring together in a patient.     

Partial 4q duplication due to inherited der(20), t(4;20)(q25;q13)mat.

A boy with mental and growth retardation associated with congenital anomalies has a partial duplication of the distal 4q chromosome region as a result of inheritance of a t(4:20) from his mother. Comparison with twelve other patients from the literature indicates that similar clinical features may be associated with this chromosome change suggesting a partial 4q duplication syndrome.     

An unbalanced translocation 46,XX,+der(18)t(18;21)(q12.2;q11.2)mat,-21 associated with maternal isodisomy 18pter-->18q12.2

We report a patient with a 46,XX,+der(18)t(18;21)(q12.2;q11.2)mat,-21 karyotype, in whom the rarely seen adjacent-2 segregation (according to the predicted pachytene diagram model) as well as two cross-overs, resulted in maternal isodisomy 18pter-->18q12.2.     

The kinases male germ cell‐associated kinase and cell cycle‐related kinase regulate kinesin‐2 motility in Caenorhabditis elegans neuronal cilia

Kinesin‐2 motors power anterograde intraflagellar transport (IFT), a highly ordered process that assembles and maintains cilia. However, it remains elusive how kinesin‐2 motors are regulated in vivo. Here, we performed forward genetic screens to isolate suppressors that rescue the ciliary defects of OSM‐3‐kinesin (homolog of mammalian homodimeric kinesin‐2 KIF17) mutants in Caenorhabditis elegans. We identified the C. elegans dyf‐5 and dyf‐18, which encode the homologs of mammalian male germ cell‐associated kinase and cell cycle‐related kinase, respectively. Using time‐lapse fluorescence microscopy, we show that DYF‐5 and DYF‐18 are IFT cargo molecules and are enriched at the distal segments of sensory cilia. Mutations of dyf‐5 and dyf‐18 generate elongated cilia and ectopic localization of the heterotrimeric kinesin‐2 (kinesin‐II) at the ciliary distal segments. Genetic analyses reveal that dyf‐5 and dyf‐18 are important for stabilizing the interaction between IFT particles and OSM‐3‐kinesin. Our data suggest that DYF‐5 and DYF‐18 act in the same pathway to promote handover between kinesin‐II and OSM‐3 in sensory cilia.