A de novo Proximal 6q Deletion Confirmed by Array Comparative Genomic Hybridization

Woo, Kwang‐Sook; Kim, Jieun; Kim, Kyung-Eun; Kim, Myo-Jing; Yoo, Jae-Ho; Ahn, Hyun-Sook; Shaffer, Lisa G.; Han, Jin‐Yeong

doi:10.3343/kjlm.2010.30.1.84

Cited by 7 publications

(5 citation statements)

References 22 publications

(27 reference statements)

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“…Among previously reported cases over 2 years of age with 6q deletion encompassing SIM1 and overlapping with that of our patient, 10 out of 12 patients had obesity. This suggests a major role of SIM1 haploinsufficiency in the pathogenesis of obesity in these subjects [Grati et al, ; Le Caignec et al, ; Klein et al, ; Zherebtsov et al, ; Bonaglia et al, ; Spreiz et al, ; Woo et al, ; Rosenfeld et al, ] (Fig. ).…”

Section: Discussionmentioning

confidence: 99%

Endocrine phenotype of 6q16.1–q21 deletion involving SIM1 and Prader–Willi syndrome‐like features

Izumi

Housam

Kapadia

et al. 2013

American J of Med Genetics Pt A

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Proximal interstitial 6q deletion involving Single-minded 1 (SIM1) gene causes a syndromic form of obesity mimicking Prader-Willi syndrome. In addition to obesity, Prader-Willi syndrome includes several other endocrinopathies, such as hypothyroidism, growth hormone deficiency, and hypogonadotropic hypogonadism. The endocrine phenotype of interstitial 6q deletion remains largely unknown, although clinical similarities between Prader-Willi syndrome and interstitial 6q deletion suggest endocrine abnormalities also may contribute to the interstitial 6q deletion phenotype. This report describes the endocrine phenotype in a propositus with the Prader-Willi-like syndrome associated with an interstitial 6q deletion including the SIM1 gene. Detailed endocrine evaluation of the propositus during childhood and adolescence revealed hypopituitarism, though initial endocrine evaluations during infancy were unremarkable. Our patient raises the possibility that hypopituitarism may be part of the phenotype, especially short stature, caused by interstitial 6q deletion. SIM1 plays an important role in the development of neuroendocrine lineage cells, implicating SIM1 haploinsufficiency in the pathophysiology of hypopituitarism seen in our propositus. Early identification of endocrine abnormalities can improve clinical outcome by allowing timely introduction of hormone replacement therapy. Hence, we suggest that detailed endocrine evaluation and longitudinal endocrine follow up be performed in individuals with proximal interstitial 6q deletion involving SIM1.

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Section: Discussionmentioning

confidence: 99%

Endocrine phenotype of 6q16.1–q21 deletion involving SIM1 and Prader–Willi syndrome‐like features

Izumi

Housam

Kapadia

et al. 2013

American J of Med Genetics Pt A

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“…3, However, few of them underwent molecular characterisation of their genetic abnormalities, using either chromosomal microarray analysis, 3,13,[15][16][17][18]22,23,25 fluorescence in situ hybridisation (FISH) analysis with bacterial artificial chromosomes (BAC) clones 21 or STR analysis. 24 Two publications evaluated genotype-phenotype correlations at the 6q16 locus, but included only five and three patients, respectively.…”

Section: Introductionmentioning

confidence: 99%

Incomplete penetrance and phenotypic variability of 6q16 deletions including SIM1

et al. 2014

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4,5,6 6q16 deletions have been described in patients with a Prader-Willi-like (PWS-like) phenotype. Recent studies have shown that certain rare single-minded 1 (SIM1) loss-of-function variants were associated with a high intra-familial risk for obesity with or without features of PWS-like syndrome. Although SIM1 seems to have a key role in the phenotype of patients carrying 6q16 deletions, some data support a contribution of other genes, such as GRIK2, to explain associated behavioural problems. We describe 15 new patients in whom de novo 6q16 deletions were characterised by comparative genomic hybridisation or single-nucleotide polymorphism (SNP) array analysis, including the first patient with fetopathological data. This fetus showed dysmorphic facial features, cerebellar and cerebral migration defects with neuronal heterotopias, and fusion of brain nuclei. The size of the deletion in the 14 living patients ranged from 1.73 to 7.84 Mb, and the fetus had the largest deletion (14 Mb). Genotype-phenotype correlations confirmed the major role for SIM1 haploinsufficiency in obesity and the PWS-like phenotype. Nevertheless, only 8 of 13 patients with SIM1 deletion exhibited obesity, in agreement with incomplete penetrance of SIM1 haploinsufficiency. This study in the largest series reported to date confirms that the PWS-like phenotype is strongly linked to 6q16.2q16.3 deletions and varies considerably in its clinical expression. The possible involvement of other genes in the 6q16.2q16.3-deletion phenotype is discussed.

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“…higher resolution techniques such as microarray-based comparative genomic hybridization (aCGH) [1][2][3][4][5][6][7][8][9][10][11].…”

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confidence: 99%

Genotype–phenotype correlation in interstitial 6q deletions: a report of 12 new cases

et al. 2012

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Interstitial deletions of 6q are associated with variable phenotypes, including growth retardation, dysmorphic features, upper limb malformations, and Prader-Willi (PW)-like features. Only a minority of cases in the literature have been characterized with high resolution techniques, making genotype-phenotype correlations difficult. We report 12 individuals with overlapping, 200-kb to 16.4-Mb interstitial deletions within 6q15q22.33 characterized by microarray-based comparative genomic hybridization to better correlate deletion regions with specific phenotypes. Four individuals have a PW-like phenotype, though only two have deletion of SIM1, the candidate gene for this feature. Therefore, other genes on 6q may contribute to this phenotype including multiple genes on 6q16 and our newly proposed candidate, the transcription cofactor gene VGLL2 on 6q22.2. Two individuals present with movement disorders as a major feature, and ataxia is present in a third. The 4.1-Mb 6q22.1q22.2 critical region for movement disorders includes the cerebellar-expressed candidate gene GOPC. Observed brain malformations include thick corpus callosum in two subjects, cerebellar vermal hypoplasia in two subjects, and cerebellar atrophy in one subject. Seven subjects' deletions overlap a ~250-kb cluster of four genes on 6q22.1 including MARCKS, HDAC2, and HS3ST5, which are involved in neural development. Two subjects have only this gene cluster deleted, and one deletion was apparently de novo, suggesting at least one of these genes plays an important role in development. Although the phenotypes associated with 6q deletions can vary, using overlapping deletions to delineate critical regions improves genotype-phenotype correlation for interstitial 6q deletions.

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A de novo Proximal 6q Deletion Confirmed by Array Comparative Genomic Hybridization

Cited by 7 publications

References 22 publications

Endocrine phenotype of 6q16.1–q21 deletion involving SIM1 and Prader–Willi syndrome‐like features

Endocrine phenotype of 6q16.1–q21 deletion involving SIM1 and Prader–Willi syndrome‐like features

Incomplete penetrance and phenotypic variability of 6q16 deletions including SIM1

Genotype–phenotype correlation in interstitial 6q deletions: a report of 12 new cases

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