Pure 6p22‐pter trisomic patient: Refined FISH characterization and genotype‐phenotype correlation

Giardino, Daniela; Finelli, Palma; Caufin, Daniele; Gottardi, Giulietta; Vasco, R. Lo; Turolla, Licia; Larizza, Lidia

doi:10.1002/ajmg.10225

Cited by 19 publications

(27 citation statements)

References 13 publications

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“…''Pure'' trisomy of the terminus of 6p (i.e., trisomy of 6p without an associated structural abnormality of another chromosome) is extremely rare, and has been reported for just five cases [Chiyo et al, 1975;Phelan et al, 1986;Rothlisberger et al, 1999;Engelen et al, 2001], including one patient that was mosaic with a 45,X cell line [Giardino et al, 2002]. We were unable to find any reports of tetrasomy of 6p.…”

Section: Discussionmentioning

confidence: 80%

“…As reviewed by Giardino et al [2002], 31 of the reported trisomy 6p cases exhibit an associated deletion of chromosomal material due an unbalanced rearrangement of a parental translocation, 10 were de novo cases, and 1 [Delatycki et al, 1999] represented direct paternal inheritance. The breakpoints associated with the terminal rearrangements span from 6p11 to 6p25, and clinical findings do not appear to be dependent upon the amount of trisomic material [Scarbrough et al, 1986].…”

Section: Discussionmentioning

confidence: 99%

“…Despite different lengths of trisomy, a characteristic phenotype has been established which includes low birth weight, developmental delay, growth retardation, craniofacial abnormalities, and congenital heart defects. Characteristic craniofacial findings include a prominent forehead, blepharophimosis, blepharoptosis, low-set or malformed ears, a small pointed chin, and a bulbous nose [Delatycki et al, 1999;Rothlisberger et al, 1999;Villa et al, 2000;Engelen et al, 2001;Giardino et al, 2002]. We present here a case of a 3-year-old girl with de novo partial tetrasomy 6p and clinical findings that correlate with cases of partial trisomy of 6p.…”

Section: Introductionmentioning

confidence: 89%

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A case of de novo partial tetrasomy of distal 6p and review of the literature

Stohler¹,

Kucharski²,

Farrow³

et al. 2007

American J of Med Genetics Pt A

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We report on a 3-year-old girl with bilateral eyelid colobomas, bulbous nose, blepharophimosis, blepharoptosis, sensorineural hearing loss, atrial septal defect, psychomotor retardation, and growth delay. Cytogenetic analysis showed additional material of unknown origin on the short arm of chromosome 8. Whole chromosome paint FISH identified the additional material to originate from chromosome 6. Subtelomeric metaphase FISH analysis detected a bright signal pattern for the 6p subtelomere probe on the derivative 8 as well as two short arm signals for the normal chromosomes 6. Interphase FISH with the 6p subtelomere probe demonstrated four 6p signals. Interestingly, metaphase FISH with a probe for the 8p subtelomere region demonstrated a signal for 8p just proximal to the translocated material. Comparative genomic hybridization studies confirmed tetrasomy of the 6p subtelomere region from 6p25.1 --> 6p25.3. Thus our patient represents the first reported case of "pure" partial tetrasomy 6p, meaning the tetrasomy was not associated with a significant deletion of chromosome arm 8p. We compare here this case with previously reported cases of partial trisomy 6p and the resulting phenotypes.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 89%

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A case of de novo partial tetrasomy of distal 6p and review of the literature

Stohler¹,

Kucharski²,

Farrow³

et al. 2007

American J of Med Genetics Pt A

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“…In particular, when pictures are available and patients are comparable in terms of sex and age, a strong physiognomic correlation was noted in cases reported by Mégarbané et al [2002], Giardino et al [2002], Pierpont et al [2000], Delatycki et al [1999], and Ferrando et al [1981]. All of these cases shared the involvement of the distal tract of 6p25pter with a proximal breakpoint that varies from 6p21.3 to p.25.…”

Section: Discussionmentioning

confidence: 90%

“…Characteristic craniofacial findings include craniosynostosis, prominent forehead, blepharophimosis and blepharoptosis, hypotelorism, low-set or malformed ears, small pointed chin, short and bulbous nose with tiny nares, choanal atresia, prominent nasal bridge, and small mouth with thin lips. Intellectual disability, epilepsy, mental retardation, autism, brain abnormalities, hearing loss, ocular defects, or immunodeficiency with susceptibility to pulmonar infections have also been reported [Smith and Pettersen, 1985;Fryns et al, 1986;Burd et al, 1988;Krassikoff and Sekhon, 1989;Katafuchi et al, 1992;Wauters et al, 1993;Giardino et al, 2002;Bart et al, 2011]. Furthermore, this chromosome anomaly is associated with a reduced life span [Villa et al, 2000;Stohler et al, 2007].…”

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confidence: 99%

Karyotype-Phenotype Correlation in Partial Trisomies of the Short Arm of Chromosome 6: A Family Case Report and Review of the Literature

Castiglione

Guaran

Astolfi

et al. 2013

Cytogenet Genome Res

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The first child (proband) of nonconsanguineous Caucasian parents underwent genetic investigation because she was affected with congenital choanal atresia, heart defects and kidney hyposplasia with mild transient renal insufficiency. The direct DNA sequencing after PCR of the CHD7 gene, which is thought to be responsible for approximately 60-70% of the cases of CHARGE syndrome/association, found no mutations. The cytogenetic analysis (standard GTG banding karyotype) revealed the presence of extrachromosomal material on 10q. The chromosome analysis was completed with array CGH (30 kb resolution), MLPA and FISH, which allowed the identification of three 6p regions (6p.25.3p23 × 3): 2 of these regions are normally located on chromosome 6, and the third region is translocated to the long arm of chromosome 10. The same chromosomal rearrangement was subsequently found in the father, who was affected with congenital ptosis and progressive hearing loss, and in the proband's sister, the second child, who presented at birth with choanal atresia and congenital heart defects. The mutated karyotypes, which were directly inherited, are thought to be responsible for a variable phenotype, including craniofacial dysmorphisms, choanal atresia, congenital ptosis, sensorineural hearing loss, heart defects, developmental delay, and renal dysfunction. Nevertheless, to achieve a complete audiological assessment of the father, he underwent further investigation that revealed an increased level of the coagulation factor XIII (300% increased activity), fluctuating levels of fibrin D-dimer degradation products (from 296 to 1,587 ng/ml) and a homoplasmic mitochondrial DNA mutation: T961G in the MTRNR1 (12S rRNA) gene. He was made a candidate for cochlear implantation. Preoperative high-resolution computed tomography and magnetic resonance imaging of the temporal bone revealed the presence of an Arnold-Chiari malformation type I. To the best of our knowledge, this study is the second report on partial 6p trisomy that involves the 10q terminal region. Furthermore, we report the first case of documented Arnold-Chiari malformation type I and increased factor XIII activity associated with 6p trisomy. We present a comprehensive report of the familial cases and an exhaustive literature review.

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Prevalence of Pathogenic Copy Number Variation in Adults With Pediatric-Onset Epilepsy and Intellectual Disability

et al. 2017

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IMPORTANCECopy number variation (CNV) is an important cause of neuropsychiatric disorders. Little is known about the role of CNV in adults with epilepsy and intellectual disability.OBJECTIVES To evaluate the prevalence of pathogenic CNVs and identify possible candidate CNVs and genes in patients with epilepsy and intellectual disability. DESIGN, SETTING, AND PARTICIPANTSIn this cross-sectional study, genome-wide microarray was used to evaluate a cohort of 143 adults with unexplained childhood-onset epilepsy and intellectual disability who were recruited from the Toronto Western Hospital epilepsy outpatient clinic from January 1, 2012, through December 31, 2014. The inclusion criteria were (1) pediatric seizure onset with ongoing seizure activity in adulthood, (2) intellectual disability of any degree, and (3) no structural brain abnormalities or metabolic conditions that could explain the seizures.MAIN OUTCOMES AND MEASURES DNA screening was performed using genome-wide microarray platforms. Pathogenicity of CNVs was assessed based on the American College of Medical Genetics guidelines. The Residual Variation Intolerance Score was used to evaluate genes within the identified CNVs that could play a role in each patient's phenotype. RESULTSOf the 2335 patients, 143 probands were investigated (mean [SD] age, 24.6 [10.8] years; 69 male and 74 female). Twenty-three probands (16.1%) and 4 affected relatives (2.8%) (mean [SD] age, 24.1 [6.1] years; 11 male and 16 female) presented with pathogenic or likely pathogenic CNVs (0.08-18.9 Mb). Five of the 23 probands with positive results (21.7%) had more than 1 CNV reported. Parental testing revealed de novo CNVs in 11 (47.8%), with CNVs inherited from a parent in 4 probands (17.4%). Sixteen of 23 probands (69.6%) presented with previously cataloged human genetic disorders and/or defined CNV hot spots in epilepsy. Eight nonrecurrent rare CNVs that overlapped 1 or more genes associated with intellectual disability, autism, and/or epilepsy were identified: 2p16.1-p15 duplication, 6p25.3-p25.1 duplication, 8p23.3p23.1 deletion, 9p24.3-p23 deletion, 10q11.22-q11.23 duplication, 12p13.33-13.2 duplication, 13q34 deletion, and 16p13.2 duplication. Five genes are of particular interest given their potential pathogenicity in the corresponding phenotypes and least tolerability to variation: ABAT, KIAA2022, COL4A1, CACNA1C, and SMARCA2. ABAT duplication was associated with Lennox-Gastaut syndrome and KIAA2022 deletion with Jeavons syndrome. CONCLUSIONS AND RELEVANCEThe high prevalence of pathogenic CNVs in this study highlights the importance of microarray analysis in adults with unexplained childhood-onset epilepsy and intellectual disability. Additional studies and comparison with similar cases are required to evaluate the effects of deletions and duplications that overlap specific genes.

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Pure 6p22‐pter trisomic patient: Refined FISH characterization and genotype‐phenotype correlation

Cited by 19 publications

References 13 publications

A case of de novo partial tetrasomy of distal 6p and review of the literature

A case of de novo partial tetrasomy of distal 6p and review of the literature

Karyotype-Phenotype Correlation in Partial Trisomies of the Short Arm of Chromosome 6: A Family Case Report and Review of the Literature

Prevalence of Pathogenic Copy Number Variation in Adults With Pediatric-Onset Epilepsy and Intellectual Disability

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