Lab Med Online.  2020 Apr;10(2):169-174. 10.3343/lmo.2020.10.2.169.

Characteristics of Interstitial Deletion in Chromosome 4q Confirmed by Array Comparative Genomic Hybridization: A Case Report and Literature Review

• Chung WY
• Lee SJ
• Kim HR
• Jun KR

• KMID: 2512249
• DOI: http://doi.org/10.3343/lmo.2020.10.2.169

Abstract

Chromosome 4q deletion syndrome is a rare disease caused by partial deletion of the long arm of chromosome 4. Phenotypic severity and expressivity vary among patients with chromosome 4q deletions, depending on the size and region of the deletion of the affected chromosome. Although there have been many reports of proximal 4q deletion cases, very few have been confirmed by high-resolution array comparative genomic hybridization (aCGH). In the current study, we presented a new case of 4q proximal deletion, with detailed genetic and clinical characteristics, and compared these characteristics to those of six previous cases with available aCGH data. According to our review, several genes known to be associated with specific phenotypes of 4q12q21.1 deletion cannot sufficiently explain the variable phenotypes observed among the cases. These phenotypes include mental retardation, microcephaly, ocular anomalies, dental anomaly, and piebaldism. Consequently, we recommend further detailed investigations into the genes associated with 4q12q21.1 deletion to assist in identifying genotype-phenotype associations more clearly.

Keyword

Chromosome 4q-syndrome; Comparative genomic hybridization; Genetic association studies

Figure

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  Fig. 1 Skeletal radiographs of the proband. (A) Both AP hand radiographs showed no fusion of the phalangeal physis’ and the bone age was considered to be in the order of 14 years, determined by the Greulich-Pyle method at the age of 17.3 years. (B) Whole spine, AP and lateral, radiographs showed minimal scoliotic curvature of the T-L spine, loss of normal lordotic curvature of the cervical spine, moderate spondylolytic spondylolisthesis at L5 on S1 (arrow), and a deformity of the anterosuperior corner of the S1 body (arrowhead). (C) AP radiographs of both feet showed deformity of the right first distal phalangeal bone (arrow). (D) Both hip AP radiographs showed sequelae of Legg-Calve-Perthes disease in the left hip, with a short, broad femoral head (arrow) and relative shortening of the left limb, in keeping with a coxa magna deformity.

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  Fig. 2 GTL-banded partial karyotype and aCGH results of the proband: 46,XY,del(4)(q12q21.1).arr[GRCh38] 4q12q21.1(53575744_76379310)x1.

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  Fig. 3 The deleted region of the proband and diagrammatic comparison of previously reported cases. (A) Significant MIM genes in the region of the 22.8-Mb deletion were detected by whole-genome SNP array in the proband. (B) The regions of previously published cases, with sufficient clinical data and confirmed by aCGH at the same loci, and DECIPHER cases of pathogenic and likely pathogenic deletions, within the deleted region of the proband.

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