Dysmorphic features and learning disability in an adult male with pure partial trisomy 17q24‐q25 due to a terminal duplication

We describe an adult male with severe learning disability, epilepsy, and dysmorphic features. Cytogenetic studies demonstrated a terminal duplication of the long arm of chromosome 17, resulting in partial trisomy 17q24‐q25. Our patient shows some of the characteristic features of the distal 17q phenotype, but in addition has more unusual features such as epilepsy, sensorineural hearing loss, and long fingers and overlapping toes. We suggest that these features occur with terminal duplications of 17q. © 2002 Wiley‐Liss, Inc.     

Distal trisomy of chromosome 17q due to inverted tandem duplication

A female infant with distal trisomy 17q is described. The anomaly resulted from a de novo inverted duplication of the 17q2405----q25.3 region as defined by high-resolution banding. The proband's overall clinical picture was in good agreement with those of previously reported cases of partial trisomy 17q. The phenotypic features relatively common to our and other reported cases, included mental and growth retardation, microcephaly, temporal retraction, blepharophimosis, saddle nose, thin upper lip, down-turned corner of the mouth, high-arched palate, low-set and deformed ears, webbed neck and lowered posterior hairline. A unique feature of the present case was systemic hirsutism.     

Mental and psychomotoric retardation in two brothers with pure partial trisomy 7q32-q34 due to a maternal insertion (14;7)

We present two brothers with mental retardation, seizures disorder, generalized muscular hypertonia, kyphoscoliosis, minor anomalies and a prominent midface. GTG-banded chromosome analysis showed a derivative chromosome 14 without clues toward the origin of the rearrangement. Microdissection of the derivative chromosome 14 and subsequent reverse painting demonstrated partial trisomy 7q32-q34 as the unbalanced product of a maternal insertion (14;7). Thus, we identified two cases with pure trisomy 7q32-q34 that allowed further delineation of this aneusomy syndrome.     

Familial short stature due to a 5q22.1-q23.2 duplication refines the 5q duplication spectrum

We identified a maternally inherited 14.2Mb duplication 5q22.1-q23.2 in two female siblings and their mother by molecular karyotyping. Both siblings were small for gestational age and presented with pronounced postnatal growth retardation, mild motor delay, congenital heart disease in one of the siblings, and distinct facial dysmorphism. As this duplication is one of the smallest reported 5q duplications, short stature and facial dysmorphism can be attributed to duplications of 5q22, whereas severe mental retardation is not part of the phenotypic spectrum of the 5q22.1-q23.2 region. Congenital heart defects, as observed in other 5q duplications, have a variable penetrance. We compared the facial features of patients with 5q duplications and found some consistent features such as high arched eyebrows, bulbous nasal tip and small lips with thin vermilion border.     

一例1q部分三体4q部分单体导致Pierre Robin序列征的遗传学分析

目的:对1例临床诊断为Pierre Robin序列征的患儿进行细胞及分子遗传学分析,寻找遗传学病因。方法:应用外周血染色体核型分析、核苷酸多态性微阵列检测和荧光原位杂交技术,分别对1例表型为下颌小、舌后坠、上呼吸道阻塞、上颚裂开、颈短的患儿及其正常表型的父母进行检测。结果:患儿核型为46,XY,der(4)add(4)...     

De novo duplication 1q32-q42: variability of phenotypic features in partial lq trisomics.

A de novo tandem duplication 1q32--q42 was observed in a 7-month-old mentally retarded and malformed male infant. Karyotype-phenotype correlation in other similar unbalanced trisomies has shown psychomotor retardation, micro- or retrognathia or both, and low set or malpositioned ears to be the most common features associated with this newly recognised syndrome. However, after reviewing patients with duplication of regions 1q2, 3, and 4 and 1q2 and 3, it was concluded that similar non-specific clinical features are also present in these 1q imbalances. On the whole, a rather wide range in phenotypical expression has been observed in different cases. Thus it is concluded that, at present, it is impossible to delineate the profile of the syndromes resulting from partial 1q trisomies.     

Novel case of dup(3q) syndrome due to a de novo interstitial duplication 3q24-q26.31 with minimal overlap to the dup(3q) critical region

Dup(3q) syndrome is characterized by typical facial features, mental and growth retardation, often with congenital heart defects. The syndrome has attracted special attention because of the clinical overlap with Cornelia de Lange syndrome (CDLS). Patients with dup(3q) syndrome are trisomic for segments of the long arm of chromosome 3, most often within the region 3q21 to 3qter. Most cases have arisen as unbalanced translocations and do involve other chromosomes also. A dup(3q) minimal region has been defined at 3q26.3-q27. We report here a 15-month-old boy with a de novo interstitial inverted duplication of 3q24-q26.31. Clinical evaluation revealed mild but typical features of dup(3q) syndrome. The duplication was characterized by conventional and molecular cytogenetics. The results allow further narrowing of the dup(3q) critical region at its distal end and suggest the existence of one or several major genes responsible for the dup(3q) syndrome in the proximal half of 3q26.31. Moreover, the results of fluorescence in situ hybridization (FISH) analysis with BAC probes suggest a disruption of the NLGN1 gene at the distal end of the duplication in 3q26.31 in the patient. The breakpoint within NLGN1 is unique for this patient, and the contribution of NLGN1 disruption to the phenotype of this patient remains unclear. Yet since NLGN1 is involved in synaptogenesis in the central nervous system, altered gene dosage is a good candidate for mental retardation as a recurrent feature of dup(3q) syndrome.     

Partial trisomy of chromosome 10(q22-q24) due to maternal insertional translocation (15;10)

Interchromosomal insertional translocations are rare chromosome rearrangements with an incidence of about 1:80,000 live births. We report on the clinical and cytogenetic findings of a newborn baby with partial trisomy 10q22-10q24 due to a maternal insertional translocation 15;10. Partial trisomy of the long arm of chromosome 10 is a distinctive chromosome aberration characterized by prenatal-onset growth retardation and craniofacial, skeletal, and other somatic anomalies. Most cases are unbalanced products from reciprocal chromosome translocations, and insertional translocations are rarely involved. The proband was initially referred because of severe intrauterine growth retardation, and fluorescence in situ hybridization (FISH) using painting probes confirmed the maternal balanced (15;10) insertion.     

Partial trisomy 22 (q11.2-q13.1) as a result of duplication and pericentric inversion.

A case of a 27 year old male with a duplication of part of the long arm of chromosome 22 (22q11.2-q13.1) together with a pericentric inversion of the same chromosome is reported. Particular phenotypic features of note include absence of speech, persistent self-injury, lack of daily living skills, colobomata, and very poor vision. Similarities between this case and other case reports of duplications of the long arm of chromosome 22 are discussed.     

Distinctive phenotype in 9 patients with deletion of chromosome 1q24-q25

Reports of individuals with deletions of 1q24→q25 share common features of prenatal onset growth deficiency, microcephaly, small hands and feet, dysmorphic face and severe cognitive deficits. We report nine individuals with 1q24q25 deletions, who show distinctive features of a clinically recognizable 1q24q25 microdeletion syndrome: prenatal-onset microcephaly and proportionate growth deficiency, severe cognitive disability, small hands and feet with distinctive brachydactyly, single transverse palmar flexion creases, fifth finger clinodactyly and distinctive facial features: upper eyelid fullness, small ears, short nose with bulbous nasal tip, tented upper lip, and micrognathia. Radiographs demonstrate disharmonic osseous maturation with markedly delayed bone age. Occasional features include cleft lip and/or palate, cryptorchidism, brain and spinal cord defects, and seizures. Using oligonucleotide-based array comparative genomic hybridization, we defined the critical deletion region as 1.9 Mb at 1q24.3q25.1 (chr1: 170,135,865-172,099,327, hg18 coordinates), containing 13 genes and including CENPL, which encodes centromeric protein L, a protein essential for proper kinetochore function and mitotic progression. The growth deficiency in this syndrome is similar to what is seen in other types of primordial short stature with microcephaly, such as Majewski osteodysplastic primordial dwarfism, type II (MOPD2) and Seckel syndrome, which result from loss-of-function mutations in genes coding for centrosomal proteins. DNM3 is also in the deleted region and expressed in the brain, where it participates in the Shank-Homer complex and increases synaptic strength. Therefore, DNM3 is a candidate for the cognitive disability, and CENPL is a candidate for growth deficiency in this 1q24q25 microdeletion syndrome.     

Partial trisomy 17q22-qter and partial monosomy Xq27-qter in a girl with a de novo unbalanced translocation due to a postzygotic error: Case report and review of the literature on partial trisomy 17qter

Partial trisomy 17q22-qter is a rare but well-recognized clinical entity. We present a case of partial trisomy for the long arm of chromosome 17, which was detected in a female infant with severe psychomotor and somatic retardation, Stargardt disease, short limbs, and numerous minor anomalies. Differential chromosomal staining demonstrated an excess of genetic material on the long arm of the late replicating X chromosome. FISH and DNA polymorphism analysis showed that the extra material belonged to the distal part of the long arm of chromosome 17 and that there was a partial monosomy of the distal part of the long arm of the derivative X chromosome. The breakpoint regions of this translocation were identified by molecular analysis using polymorphic microsatellite markers on human chromosomes 17 and X. The origin of the abnormal X chromosome was found to be paternal, whereas the origin of the duplicated part of chromosome 17 was maternal. The unbalanced translocation between the paternal X and the maternal chromosome 17 is, therefore, suggested to be due to a postzygotic error. Am. J. Med. Genet. 70:87–94, 1997. © 1997 Wiley-Liss, Inc.     

Mental and psychomotoric retardation in two brothers with pure partial trisomy 7q32‐q34 due to a maternal insertion (14;7)

We present two brothers with mental retardation, seizures disorder, generalized muscular hypertonia, kyphoscoliosis, minor anomalies and a prominent midface. GTG‐banded chromosome analysis showed a derivative chromosome 14 without clues toward the origin of the rearrangement. Microdissection of the derivative chromosome 14 and subsequent reverse painting demonstrated partial trisomy 7q32–q34 as the unbalanced product of a maternal insertion (14;7). Thus, we identified two cases with pure trisomy 7q32–q34 that allowed further delineation of this aneusomy syndrome. Am. J. Med. Genet. 91:291–297, 2000. © 2000 Wiley‐Liss, Inc.     

Trisomy 2q35-q37 due to insertion of 2q material into 17q25: clinical, cytogenetic, and molecular cytogenetic characterization

We present a 7-year-old boy with growth retardation, developmental and mental delay, and minor physical abnormalities. The patient had a male karyotype with duplicated material of unknown origin in the long arm of chromosome 17. The origin of the duplicated material was clarified by fluorescence in situ hybridization. Forward chromosome painting showed that the extra material originated from chromosome 2, which was inserted into 17q25. Further characterization of the aberrant chromosome 17 by microdissection and reverse chromosome painting revealed a duplication of bands 2q35 to q37.1. To our knowledge, no other individual with a duplication of this small segment has been described so far. The clinical findings of 13 cases with isolated trisomy 2q are reviewed in relation to the size of the duplicated region. Functional analysis of the duplicated 2q region suggests that critical loci for visceral and central nervous system development in distal trisomy 2q are proximal to 2q33.