Duplication dup(1)(q41q44) defined by fluorescence in situ hybridization: delineation of the 'trisomy 1q42-->qter syndrome'

We report on a novel case of pure partial tandem duplication 1q42q43 confirmed by fluorescence in situ hybridization (FISH). We compare the manifestations of our patient with similar cases previously reported. We conclude that the most common clinical manifestations of trisomy 1q42qter are prenatal and postnatal growth retardation, relative macrocephaly, triangular face, prominent forehead, broad nasal bridge, abnormal philtrum, micro/retrognathia, cardiac defects and mental retardation. We would like to emphasize the importance of the FISH technique in the identification of the duplicated segment.     

De novo deletion of 1q31.1-q32.1 in a patient with developmental delay and behavioral disorders

We describe the case of a 6-year-old boy with a de novo deletion of the long arm of chromosome 1 encompassing band 1q31.1-q32.1, minor facial anomalies, mild developmental delay, and behavioral disorders. His postnatal karyotype was normal. Using array-comparative genomic hybridization, we identified and characterized a de novo 1q interstitial deletion of about 15.6 Mb, which partially overlaps those of other reported cases. We considered the gene content of the deleted region in an attempt to compare the clinical features of our patient with these other cases, even though they were not characterized molecularly in detail. The most remarkable difference was the absence of microcephaly. To the best of our knowledge, this is the first report of a de novo 1q31.1-q32.1 deletion. Moreover, it illustrates how molecular delineation associated with fine clinical characterization can improve the genotype-phenotype correlations of classical cytogenetic abnormalities.     

8q24.12 Interstitial deletion in trichorhinophalangeal syndrome type I

Summary In the present report we present the first example of a small interstitial 8q24.12 deletion in a patient with trichorhinophalangeal syndrome type I.     

Interstitial deletion of the band 4p15.3 defined by sequential replication banding

A 15-year-old boy with intellectual disability was found to have a de novo interstitial deletion in the short arm of chromosome 4. Using GTL banding and sequential replication banding the deleted band was found to be the more terminal of the two G dark sub-bands of 4p15, that is 4p15.3. The karyotype was defined as 46,XY,del(4)(p15.2p16.100). To our knowledge this specific deletion has not been previously described.     

Terminal deletion of (1)(q42) and its phenotypical manifestations

Summary A 5-year-old male with multiple malformations (dwarfism, microcephalia with brachycephalic shape of skull, mongoloid lid axis, epicanthus, convergent strabismus, flat root of the nose, micrognathia, missing uvula, deformed low-set ears, hypoplastic genitals, and general hypotonia), severe mental retardation, and cerebral paroxysms caused by a partial monosomy (1)(q42qter) is described. This case is compared with other cases with a partial monosomy or ring-1 chromosomes.To whom offprint requests should be sent     

Interstitial deletion of a chromosome 7 (q11.2q22.1) in a child with splithand/splitfoot malformation

Report on a 2-year-old, severely retarded girl with partial monosomy of 7q who exhibited not only features possibly due to the chromosomal aberration such as intrauterine dystrophy, microcephaly, odd facies, cleft palate, CHD, but also typical splithand/splitfoot malformation.     

Interstitial deletion of 16(q13q22) in a newborn resulting from a paternal insertional translocation.

A dysmorphic newborn showed an interstitial deletion of the long arm of a chromosome 16 due to a balanced paternal insertional translocation 46,XY,ins(14;16)(q23;q13q22). The insertion was confirmed by chromosomal in situ suppression (CISS-) hybridization. Clinical features considered to be typical for a 16q- phenotype are demonstrated in this patient. Similar observations described in the literature are compared and discussed with reference to the phenocritical region.     

Homozygosity mapping of the gene for Chediak-Higashi syndrome to chromosome 1q42-q44 in a segment of conserved synteny that includes the mouse beige locus (bg).

Chediak-Higashi syndrome (CHS) is an autosomal recessive disorder characterized by hypopigmentation or oculocutaneous albinism and severe immunologic deficiency with neutropenia and lack of natural killer (NK) cell function. Most patients die in childhood from pyogenic infections or an unusual lymphoma-like condition. A hallmark of the disorder is giant inclusion bodies seen in all granule-containing cells, including granulocytes, lymphocytes, melanocytes, mast cells, and neurons. Similar ultrastructural abnormalities occur in the beige mouse, which thus has been suggested to be homologous to human CHS. High-resolution genetic mapping has indicated that the bg gene region of mouse chromosome 13 is likely homologous to the distal portion of human chromosome 1q. Accordingly, we carried out homozygosity mapping using markers derived from distal human chromosome 1q in four inbred families or probands with CHS. Our results indicate that the human CHS gene maps to an 18.8-cM interval in chromosome segment 1q42-q44 and that human CHS therefore is very likely homologous to mouse bg.     

Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders

Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally expressed imprinted genes in the contribution of Copy Number Variants (CNVs) at this interval to the incidence of psychotic illness. This work will have tangible benefits for patients with 15q11.2-q13.3 duplications by aiding genetic counseling.     

Terminal deletion 1q43 in a newborn with hydrocephalus

A male newborn presented the main craniofacial features of the 1q terminal syndrome: prominent metopic sutures, flat nose bridge, wide short nose with anteverted nares, epicantus, telecanthus, long philtrum, thin upper lip with a well defined cupid bow, downturned corners of the mouth, retrognathia. The child also had an aqueductal obstructive hydrocephalus.     

Small terminal 10q26 deletion in a male patient with Noonan-like stigmata: diagnosis by cytogenetic and FISH analysis

A male patient is reported with terminal 10q26 deletion, developmental retardation, special behaviour, and multiple clinical anomalies including hypotonia, short stature of postnatal onset, short webbed neck, craniofacial dysmorphism, pectus excavatum with widely spaced small nipples, cryptorchidism with scrotal hypoplasia, limb and musculoskeletal anomalies. The facial dysmorphism mainly consisted of trigonocephaly, a long, triangular and asymmetrical face, hypertelorism with pseudoepicanthus, broad nasal bridge, high-arched palate, retrognathia, low-set dysplastic auricles and, on ophthalmologic examination, strabismus, astigmatism and myopia. Some of these clinical stigmata were suggesting the diagnosis of Noonan syndrome. The extremities showed special features including shortening of proximal limbs, brachydactyly with syndactyly of toes II-III and left fingers III-IV, hypoplastic toenails and joint abnormalities. A diastasis of abdominal muscles was noted and, on X-rays a thoracic scoliosis and bilateral coxa valga were evidenced. Analyses of G- and T-banded chromosomes complemented by FISH analyses using different subtelomere probes detected a terminal 10q26 deletion. Subsequent FISH studies using different probes of the 10q26 region were performed in an attempt to closely define the breakpoint and the extent of the deletion and, thereby, to allow karyotype/phenotype comparison between this patient and a previously reported case with an apparently similar 10q26 deletion.     

Distal trisomy of 10q. Report of a new case of duplication 10q25.2-25.3-->qter defined by FISH

In the present work, we report on a 2.5-year-old male patient with typical clinical features of partial trisomy of the distal third of chromosome 10 long arm. The karyotype was: 46,XY, dir dup(10)(q25.2-25.3-->qter). The identification of the duplicated segment was carried out by the fluorescence in situ hybridization technique using region-specific probes. The proband's phenotype is compared with previously reported cases.     

Association of a new chromosomal deletion [del(1)(q32q42)] with diaphragmatic hernia: assignment of a human ferritin gene

Summary A newborn male with a large diaphragmatic hernia presented in severe respiratory distress. Additional features included a paucity of subcutaneous tissue, mild facial dysmorphism, webbing of the neck, genital hypoplasia, and flexion contractures of the fingers. His karyotype showed a previously unreported de novo interstitial deletion of the long arm of chromosome 1[46,XY,de(1)(pterq32.3::q42.3qter)]. Regional mapping of five human genes that have been provisionally assigned to chromosome 1 was performed by restriction analysis of genomic DNA from this patient. Glucocerebrosidase, H4 histone, renin, and alpha-spectrin genes mapped outside the delected region, whereas an H subunit of the ferritin gene mapped to 1q32q42. These results indicate the utility of chromosomal deletions in gene mapping, and the importance of karyotype analysis in newborns with diaphragmatic hernias.