Interstitial 6q deletion and Prader‐Willi‐like phenotype

Stein, Constance K.; Stred, Susan E.; Thomson, Laura L.; Smith, Frank C.; Hoo, Joe J.

doi:10.1111/j.1399-0004.1996.tb03794.x

Cited by 36 publications

(20 citation statements)

References 17 publications

(13 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Deletion of SIM1 at 6q16.3 has been proposed as the cause of a Prader-Willi (PW)-like phenotype in some individuals with interstitial 6q deletions [11,[16][17][18][19][20][21]. In contrast, there has been a single case report of an individual with a PW-like phenotype whose 6q22.2q23.1 deletion likely did not include SIM1, nor did it overlap with other deletions associated with this phenotype [22]. Furthermore, two individuals with more proximal 6q14.1q15 deletions have been reported with a PW-like phenotype [10].…”

mentioning

confidence: 80%

“…The five previously reported individuals with seizures had cytogenetically defined deletions that overlapped at 6q22.2q22.32 [12,14,22,68,69], while four individuals have been reported with EEG abnormalities without seizures and molecularly defined deletions involving 6q16, though they do not all overlap each other [1,7,16] (Fig. 2a).…”

Section: Seizures In 6q Deletionsmentioning

confidence: 91%

“…Subject 3 has a progressive tremor. Other individuals have been reported with interstitial 6q deletions and ataxia or myopathy [2, 16,17,19,22,68,69], most of whom also had either seizures or a PW-like phenotype (Fig. 5).…”

Section: Movement Disorders In 6q Deletionsmentioning

confidence: 97%

See 2 more Smart Citations

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

et al. 2012

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 80%

Section: Seizures In 6q Deletionsmentioning

confidence: 91%

See 1 more Smart Citation

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

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The incidence is 1/15-25,000 per live births. Early-onset obesity in combination with a developmental disorder was recently also reported in patients with a deletion at 16p11.2 [Bochukova et al, 2010;Walters et al, 2010] and has also been observed in a majority of patients with deletions within the 6q15-q23.1 region [Turleau et al, 1988;Villa et al, 1995;Stein et al, 1996;Gilhuis et al, 2000;Faivre et al, 2002;Varela et al, 2006;Bonaglia et al, 2008].…”

Section: Discussionmentioning

confidence: 99%

“…In the reported cases with deletions at chromosome 6q, there are large phenotypic variations due to differences in the size and location of the deletion [Turleau et al, 1988;Villa et al, 1995;Stein et al, 1996;Hopkin et al, 1997;Gilhuis et al, 2000;Faivre et al, 2002;Grati et al, 2005;Le Caignec et al, 2005;Varela et al, 2006;Klein et al, 2007;Bonaglia et al, 2008]. In a review of 60 patients by Hopkin et al [1997], 3 distinct phenotypes were described on the basis of the location of the 6q deletion.…”

Section: Introductionmentioning

confidence: 99%

Interstitial Deletions at 6q14.1–q15 Associated with Obesity, Developmental Delay and a Distinct Clinical Phenotype

Wentzel

Lynch²,

Stattin³

et al. 2010

Mol Syndromol

View full text Add to dashboard Cite

Background: Interstitial deletions of the long arm of chromosome 6 have been described in several patients with obesity and a Prader-Willi-like phenotype. Haploinsufficiency of the SIM1 gene located at 6q16.3 is suggested as being responsible for the regulation of body weight. Here we report on 2 patients with interstitial deletions at 6q14.1–q15 presenting with obesity and symptoms strikingly similar to those reported for deletions involving the SIM1 gene despite not having a deletion of this gene. Methods: Array comparative genomic hybridisation was used to diagnose 2 children with obesity and developmental delay, revealing 2 interstitial deletions at 6q14.1–q15 of 8.73 and 4.50 Mb, respectively, and a region of overlap of 4.2-Mb. Results: The similar phenotype in the 2 patients was most likely due to a 4.2-Mb common microdeletion at 6q14.1–q15. Another patient has previously been described with an overlapping deletion. The 3 patients share several features, such as developmental delay, obesity, hernia, rounded face with full cheeks, epicanthal folds, short palpebral fissures, bulbous nose, large ears, and syndactyly between toes II and III. Conclusions: Together with a previously reported patient, our study suggests that the detected deletions may represent a novel clinically recognisable microdeletion syndrome caused by haploinsufficiency of dosage-sensitive genes in the 6q14.1–q15 region.

show abstract

Prader-Willi-like syndrome in a patient with an Xq23q25 duplication

1998

View full text Add to dashboard Cite

We report on a 24-year old woman with an Xq duplication and findings suggestive of Prader-Willi syndrome (PWS). Her birth weight was at the 3rd centile and her birth length was less than the 3rd centile. She was hypotonic and had a weak cry as an infant. There were no feeding difficulties, although her mother reports that as an infant, she was "small for her age." Excessive weight gain began between 3 and 4 years. The patient's development was delayed and she received special education. She has a history of hiding food. She has a sleep disturbance disorder and inappropriate social behavior. At the age of 24 years her height was below the 5th centile and weight >>95th centile. She has physical findings typical of PWS, skin picking, and speech articulation defects. Cytogenetic analysis showed a 46,X,dup(X)(q23q25) karyotype. Fluorescent in situ hybridization (FISH) studies using a chromosome X painting probe demonstrated that the rearrangement was intrachromosomal. The X-chromosome fold scoring technique was used to determine the X inactivation pattern and indicated that some cells expressed the abnormal X chromosome. Results of FISH studies using the SNRPN probe localized to 15q11q13 and DNA studies using the PW71B and SNRPN probes were normal. The duplicated X chromosome, random X inactivation pattern, and the negative molecular studies for PWS indicate that the abnormal X chromosome is the basis of this patient's phenotype. This patient emphasizes the importance of obtaining a karyotype even when a syndrome diagnosable by molecular methods is strongly suspected.

show abstract

Interstitial 6q deletion and Prader‐Willi‐like phenotype

Cited by 36 publications

References 17 publications

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

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

Interstitial Deletions at 6q14.1–q15 Associated with Obesity, Developmental Delay and a Distinct Clinical Phenotype

Prader-Willi-like syndrome in a patient with an Xq23q25 duplication

Contact Info

Product

Resources

About