Clinical and genomic characterization of distal duplications and deletions of chromosome 4q: Study of two cases and review of the literature

Rossi, Michael R.; DiMaio, Miriam S.; Xiang, Bixia; Lu, Kangmo; Kaymakçalan, Hande; Seashore, Margretta R.; Mahoney, Maurice J.; Li, Peining

doi:10.1002/ajmg.a.33088

Cited by 49 publications

(63 citation statements)

References 23 publications

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“…Terminal and interstitial deletions of the distal segment of the long arm of chromosome 4 (Cr4q del) are not common genetic disorders with an estimated incidence of 1/100,000 1 . The first report was presented by Ockey et al in 1967 2 , whereas in 1992 a large interstitial Cr4q del with breakpoints at q31.22 to q34.2 was described by Sarda and colleagues 3 .…”

Section: Introductionmentioning

confidence: 99%

Pain insensitivity in a child with a de novo interstitial deletion of the long arm of the chromosome 4: Case report

Cascella

Muzio

2017

Rev. chil. pediatr.

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Introduction. Terminal and interstitial deletions of the distal segment of the long arm of chromosome 4 (Cr4q del) are not common genetic disorders. The severity of the phenotype is correlated with the size of the deletion because small deletions have little clinical impact, whereas large deletions are usually associated with multiple congenital anomalies, postnatal growth failure, and moderate to severe intellectual disability. Alteration in pain tolerance has not been included among these features, also in case of large deletions. The purpose of this report is to document a case of a child affected by interstitial Cr4q del, expressing pain insensitivity as clinical feature not previously described. We also offer a discussion on genetic disorders featuring pain insensitivity/indifference. Case report. A Caucasian girl aged 12 came to our observation for a developmental delay with multiple congenital abnormalities and moderate intellectual disability (IQ 47). A de novo interstitial Cr4 del between band q31.3 and q32.2 (Cr4 del q31.3 to q32.2) was found. The child also expresses no evidence of pain perception to injures which normally evoke pain. Consequently, she is affected by severe disability caused by painless injuries and self-injurious behaviours, such as excessive self-rubbing and scratching. The neurological examination manifested high pain threshold with preserved tactile sensitivity. Conclusions. This is the first report of pain insensitivity in a patient with a specific genetic deletion involving the interstitial region of the distal long arm of Cr4. Moreover, this report could serve as a useful model to better understand mechanisms of pain perception and its modulation.

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Section: Introductionmentioning

confidence: 99%

Pain insensitivity in a child with a de novo interstitial deletion of the long arm of the chromosome 4: Case report

Cascella

Muzio

2017

Rev. chil. pediatr.

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“…The contiguous deletion and duplication patterns have also been reported in a proportion of ring chromosomes 13, 15, 18, 20, 21, and 22 [Rossi et al, 2008;Conlin et al, 2011] and in cases with subtelomeric abnormalities of 8p, 4q, 5p, and other chromosomes [Xiang et al, 2008;Rossi et al, 2009;Yu et al, 2010]. A chromosomal inverted duplication with a terminal deletion has been induced by segmental duplications such as the 2 olfactory receptor gene clusters flanking a 5-Mb region of 8p23.1 [Yu et al, 2010].…”

Section: Discussionmentioning

confidence: 95%

Unique Genomic Structure and Distinct Mitotic Behavior of Ring Chromosome 21 in Two Unrelated Cases

Zhang

Xu²,

Seashore³

et al. 2012

Cytogenet Genome Res

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A ring chromosome replacing a normal chromosome could involve variable structural rearrangements and mitotic instability. However, most previously reported cases lacked further genomic characterization. High-resolution oligonucleotide array comparative genomic hybridization with single-nucleotide polymorphism typing (aCGH+SNP) was used to study 2 unrelated cases with a ring chromosome 21. Case 1 had severe myopia, hypotonia, joint hypermobility, speech delay, and dysmorphic features. aCGH detected a 1.275-Mb duplication of 21q22.12–q22.13 and a 6.731-Mb distal deletion at 21q22.2. Case 2 showed severe growth and developmental retardations, intractable seizures, and dysmorphic features. aCGH revealed a contiguous pattern of a 3.612- Mb deletion of 21q22.12–q22.2, a 4.568-Mb duplication of 21q22.2–q22.3, and a 2.243-Mb distal deletion at 21q22.3. Mitotic instability was noted in 13, 30, and 76% of in vitro cultured metaphase cells, interphase cells, and leukocyte DNA, respectively. The different phenotypes of these 2 cases are likely associated with the unique genomic structure and distinct mitotic behavior of their ring chromosome 21. These 2 cases represent a subtype of ring chromosome 21 probably involving somatic dicentric ring breakage and reunion. A cytogenomic approach is proposed for characterizing the genomic structure and mitotic instability of ring chromosome abnormalities.

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“…Genomic delineation of chromosomally observed complex structural rearrangements and heterogeneous interstitial and subtelomeric imbalances allows fine-mapping of critical regions or intervals to identify potential candidate dosage-sensitive genes [4,5]. Cytogenomic analysis also resolves the genomic structures, mutagenesis mechanisms and mitotic or meiotic behaviors from puzzling chromosomal structural abnormalities like ring chromosomes or supernumerary marker chromosomes.…”

Section: Cytogenomic Abnormalities In Intellectual and Developmental mentioning

confidence: 99%

Clinical and genomic characterization of distal duplications and deletions of chromosome 4q: Study of two cases and review of the literature

Cited by 49 publications

References 23 publications

Pain insensitivity in a child with a de novo interstitial deletion of the long arm of the chromosome 4: Case report

Pain insensitivity in a child with a de novo interstitial deletion of the long arm of the chromosome 4: Case report

Unique Genomic Structure and Distinct Mitotic Behavior of Ring Chromosome 21 in Two Unrelated Cases

Cytogenomic Abnormalities and Underlying Mechanisms for Intellectual and Developmental Disabilities

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