Interstitial 6q deletion with a Prader--Willi-like phenotype: a new case and review of the literature

doi:10.1053/ejpn.1999.0259

European Journal of Paediatric Neurology

Volume 4, Issue 1, January 2000, Pages 39-43

https://doi.org/10.1053/ejpn.1999.0259 Get rights and content

Abstract

We report on an additional fourth case of Prader–Willi (PW)-like phenotype and an interstitial deletion of 6q. Despite sharing clinical characteristics, patients with a PW-like phenotype and a deletion of 6q, have features which distinguish them from Prader–Willi syndrome (PWS) patients. This case emphasizes the need to examine patients with suspected PWS, but who are negative for recognizable deletions of 15q11–q13 or uniparental maternal disomy of chromosome 15, for a deletion of 6q.

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Associations between the clinical findings of cases having submicroscopic chromosomal imbalances at chromosomal breakpoints of apparently balanced structural rearrangements
2017, Gene Reports
Citation Excerpt :
Therefore, the 5HT-1B gene appears as a good candidate for the intellectual disability observed in our patient. Several deletions of 6q16.2, included the Single-Minded Family BHLH Transcription Factor 1 (SIM1) gene, have been identified in obese patients presenting with a Prader-Willi–like (PWL-like) syndrome (Gilhuis et al., 2000), which is characterized in early infancy by global developmental delay, hypotonia, and feeding difficulties and, later in life, by hyperphagia, obesity, and facial dysmorphisms (Bonaglia et al., 2008). Wentzel et al. (2010) described two patients with interstitial deletions at 6q14.1–q15 that each displayed obesity and clinical findings similar to those reported for deletions involving the SIM1 gene, yet with no deletion of this gene due to a difference in the location of the deleted region (Wentzel et al., 2010).
Although the carriers with apparently balanced structural rearrangements have usually normal phenotype, phenotypical abnormalities can be seen in approximately 6% de novo cases. A number of different mechanisms are involved in the appearance of these phenotypic abnormalities, one of which is submicroscopic chromosomal imbalances at chromosomal breakpoints. Our goal was to unravel the possible submicroscopic chromosomal imbalances at chromosomal breakpoints by using array-CGH analysis in patients with apparently balanced structural rearrangements and to link these to the clinical findings. A total of nine patients with reciprocal translocation carriers (2 familial, 7 de novo) and six patients with inversion carriers (2 familial, 4 de novo) were included in this study. In order to evaluate the possible microdeletions and microduplications at the chromosomal breakpoints, DNA samples were isolated from the peripheral blood of the patients (and their parents) and investigated using array-CGH analysis. Array-CGH analysis revealed submicroscopic chromosomal imbalances at breakpoints in 3 of the 7 (43%) de novo reciprocal translocation carriers. Additionally, 1 out of 4 (25%) de novo inversion carriers were found to have a submicroscopic chromosomal imbalance in unrelated chromosome seen in cytogenetic analysis. Furthermore, no submicroscopic chromosomal imbalances were detected in either of the two familially transmitted reciprocal translocation carriers. Based on the results of both array-CGH analysis and conventional cytogenetic analysis, the karyotypes of the patients were designated as follows:
46,XY,t(13;16)(q14;q12.1)dn.arr[hg19]13q14.2-q21.1(50,131,521–57,306,322)x1dn; 46,XY,t(6;9)(q13;p12)dn.arr[hg19]6q14.1(78,016,882–83,293,127),9p23p22.3(12,249,507–15,939,627)x1dn;
46,XX,t(X;16)(p11.21;p11.2)dn.arr[hg19]Xp11.22(50,367,783–50,441,087)x3dn; 46,XX,inv.(18)(p11.23q11.2)dn.arr[hg19]22q11.21(18,706,001–21,505,417)x1mat.
Our results demonstrate the necessity of using array-CGH to evaluate patients with apparently balanced structural rearrangements in order to determine the submicroscopic chromosomal imbalances at chromosomal breakpoints that are related to the observed clinical abnormalities.
DNA sequencing and copy number variation analysis of MCHR2 in a cohort of Prader Willi like (PWL) patients
2018, Obesity Research and Clinical Practice
Citation Excerpt :
Noteworthy, PWL (and subsequently PWS) also shares clinical characteristics (obesity and intellectual disability) with the chromosome 16p11.2 deletion syndrome, which has been reported as a cause of obesity [23]. In literature, deletions at chromosome 6q are most frequently reported in association with PWL which led to the suggestion of haploinsufficiency (presence of only one active copy) of the single-minded 1 (SIM1) gene at 6q16.3 as a possible cause for the presence of obesity in these patients [6,8–20]. However, our own research showed a limited involvement of copy number and sequence variation in SIM1 in the PWL phenotype [24].
Prader Willi Syndrome (PWS) is a syndromic form of obesity caused by a chromosomal aberration on chromosome 15q11.2–q13. Patients with a comparable phenotype to PWS not carrying the 15q11.2–q13 defect are classified as Prader Willi like (PWL). In literature, PWL patients do frequently harbor deletions at 6q16, which led to the identification of the single-minded 1 (SIM1) gene as a possible cause for the presence of obesity in these patients. However, our previous work in a PWL cohort showed a rather limited involvement of SIM1 in the obesity phenotype. In this paper, we investigated the causal role of the melanin-concentrating hormone receptor 2 (MCHR2) gene in PWL patients, as most of the reported 6q16 deletions also encompass this gene and it is suggested to be active in the control of feeding behavior and energy metabolism.
Copy number variation analysis of the MCHR2 genomic region followed by mutation analysis of MCHR2 was performed in a PWL cohort.
Genome-wide microarray analysis of 109 patients with PWL did not show any gene harboring deletions on chromosome 6q16. Mutation analysis in 92 patients with PWL demonstrated three MCHR2 variants: p.T47A (c.139A > G), p.A76A (c.228T > C) and c.*16A > G. We identified a significantly higher prevalence of the c.228T > C C allele in our PWL cohort compared to previously published results and controls of the ExAC Database.
Overall, our results are in line with some previously performed studies suggesting that MCHR2 is not a major contributor to human obesity and the PWL phenotype.
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Case studyInterstitial 6q deletion with a Prader--Willi-like phenotype: a new case and review of the literature

Abstract

Case study
Interstitial 6q deletion with a Prader--Willi-like phenotype: a new case and review of the literature