Lab Med Online.  2020 Jul;10(3):255-261. 10.3343/lmo.2020.10.3.255.

Beckwith-Wiedemann Syndrome and Jacobsen Syndrome Caused by 11pter Duplication and 11qter Deletion Inherited from Paternal Pericentric Inversion

• Choi WK
• Lim SE
• Kim GH
• Lee BH
• Seol CA
• Seo EJ

• KMID: 2504138
• DOI: http://doi.org/10.3343/lmo.2020.10.3.255

Abstract

We report a case of Beckwith-Wiedemann syndrome (BWS) and Jacobsen syndrome (JBS) due to 11pter trisomy and 11qter monosomy caused by paternal inv(11)(p15.1q24.2). The patient was born premature and had a variety of clinical features including characteristic facial dysmorphism, cardiac abnormalities, and thrombocytopenia. The karyotype was described as 46,XX,rec(11)dup(11p)inv(11)(p15.1q24.2)pat and methylation-specific multiplex ligation-dependent probe amplification analysis showed duplication of the 11p15.5 region and hypermethylation of imprinting center 1. Chromosomal microarray analysis demonstrated 23.8 Mb duplication on 11pter-p14.3 and 13.8 Mb deletion on 11q23.3-qter. These results were consistent with BWS and JBS, respectively. Because uniparental disomy inherited from paternal pericentric inversion results in simultaneous 11p15.5 duplication and 11q23.3 deletion, appropriate genetic tests are necessary for accurate genetic diagnosis of patients.

Keyword

Beckwith-Wiedemann syndrome; Jacobsen syndrome; Pericentric inversion; 11pter duplication; 11qter deletion; Chromosomal microarray

Figure

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  Fig. 1 Karyogram and partial image of chromosome 11 in patient (A) and patient’s father (B).

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  Fig. 2 Capillary electrophoresis electropherogram of MS-MLPA for 11p15.5 region. The red peak represents control DNA amplification. The blue peak represents the patient’s DNA amplification. (A) Detection of copy number change without HhaI enzyme. Peak heights of all probes targeting H19 and KCNQ1OT1 increased, showing duplication of H19 and KCNQ1OT1. (B) Detection of methylation status with HhaI enzyme. The red arrows indicate increased peak heights of probes targeting H19, showing hypermethylation of imprinting center 1. Abbreviation: MS-MLPA, methylation-specific multiplex ligation-dependent probe amplification.

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  Fig. 3 Duplication and deletion at 11p and11q in this patient demonstrated by chromosomal microarray. The blue bar and red bar indicate duplication and deletion regions, respectively. The chromosomal microarray of chromosome 11 showed a 23.8 Mb duplication at 11p15.5p14.3 and a 13.8 Mb deletion at 11q23.3q25.

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