Co-occurrence of genomic imbalances on Xp22.1 in the SHOX region and 15q25.2 in a girl with short stature, precocious puberty, urogenital malformations and bone anomalies
Abstract Background Mutations of SHOX represent the most frequent monogenic cause of short stature and related syndromes. The genetic alterations include point mutations and deletions/duplications spanning both SHOX and its regulatory regions, although microrearrangements are confined to either the...
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | BMC Medical Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12920-018-0445-8 |
| _version_ | 1818439910085885952 |
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| author | Alice Monzani Deepak Babu Simona Mellone Giulia Genoni Antonella Fanelli Flavia Prodam Simonetta Bellone Mara Giordano |
| author_facet | Alice Monzani Deepak Babu Simona Mellone Giulia Genoni Antonella Fanelli Flavia Prodam Simonetta Bellone Mara Giordano |
| author_sort | Alice Monzani |
| collection | DOAJ |
| description | Abstract Background Mutations of SHOX represent the most frequent monogenic cause of short stature and related syndromes. The genetic alterations include point mutations and deletions/duplications spanning both SHOX and its regulatory regions, although microrearrangements are confined to either the downstream or upstream enhancers in many patients. Mutations in the heterozygous state have been identified in up to 60–80% of Leri-Weill Dyschondrosteosis (LWD; MIM #127300) and approximately 4–5% of Idiopathic Short Stature (ISS; MIM#300582) patients. Homozygous or compound heterozygous mutations as well as biallelic deletions of SHOX and/or the enhancer regions result in a more severe phenotype, which is known as Langer Mesomelic Dysplasia (LMD; MIM #249700). Case presentation A 17 year old girl, presented with severe short stature, growth hormone deficiency (GHD), precocious puberty, dorsal scoliosis, dysmorphisms and urogenital malformations. She was born with agenesis of the right tibia and fibula, as well as with a supernumerary digit on the left foot. Array comparative genomic hybridization (aCGH) analysis detected the presence of two distinct duplications on Xp22.1 flanking the SHOX coding sequence and involving its regulatory regions. An additional duplication of 1.6–2.5 Mb on 15q25.2 that included 13 genes was also identified. The girl was adopted and the parent’s DNA was not available to establish the origin of the chromosome imbalances. Conclusions The complex phenotype observed in our patient is probably the result of the co-occurrence of rearrangements on chromosomes Xp22.1 and 15q25.2. The duplicated region on 15q25.2 region is likely to contain dosage-sensitive genes responsible for some of the clinical features observed in this patient, whereas the extreme short stature and the skeletal anomalies are likely attributable to the comorbidity of GHD and copy number variants in the SHOX region. |
| first_indexed | 2024-12-14T18:03:58Z |
| format | Article |
| id | doaj.art-ed50ad52839b4ec9b6f469eca4213fd4 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-12-14T18:03:58Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
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| series | BMC Medical Genomics |
| spelling | doaj.art-ed50ad52839b4ec9b6f469eca4213fd42022-12-21T22:52:24ZengBMCBMC Medical Genomics1755-87942019-01-011211510.1186/s12920-018-0445-8Co-occurrence of genomic imbalances on Xp22.1 in the SHOX region and 15q25.2 in a girl with short stature, precocious puberty, urogenital malformations and bone anomaliesAlice Monzani0Deepak Babu1Simona Mellone2Giulia Genoni3Antonella Fanelli4Flavia Prodam5Simonetta Bellone6Mara Giordano7Division of Pediatrics, Department of Health Sciences, Università del Piemonte OrientaleLaboratory of Human Genetics, Department of Health Sciences, Università del Piemonte OrientaleLaboratory of Human Genetics, Department of Health Sciences, Università del Piemonte OrientaleDivision of Pediatrics, Department of Health Sciences, Università del Piemonte OrientaleLaboratory of Human Genetics, Department of Health Sciences, Università del Piemonte OrientaleDivision of Pediatrics, Department of Health Sciences, Università del Piemonte OrientaleDivision of Pediatrics, Department of Health Sciences, Università del Piemonte OrientaleLaboratory of Human Genetics, Department of Health Sciences, Università del Piemonte OrientaleAbstract Background Mutations of SHOX represent the most frequent monogenic cause of short stature and related syndromes. The genetic alterations include point mutations and deletions/duplications spanning both SHOX and its regulatory regions, although microrearrangements are confined to either the downstream or upstream enhancers in many patients. Mutations in the heterozygous state have been identified in up to 60–80% of Leri-Weill Dyschondrosteosis (LWD; MIM #127300) and approximately 4–5% of Idiopathic Short Stature (ISS; MIM#300582) patients. Homozygous or compound heterozygous mutations as well as biallelic deletions of SHOX and/or the enhancer regions result in a more severe phenotype, which is known as Langer Mesomelic Dysplasia (LMD; MIM #249700). Case presentation A 17 year old girl, presented with severe short stature, growth hormone deficiency (GHD), precocious puberty, dorsal scoliosis, dysmorphisms and urogenital malformations. She was born with agenesis of the right tibia and fibula, as well as with a supernumerary digit on the left foot. Array comparative genomic hybridization (aCGH) analysis detected the presence of two distinct duplications on Xp22.1 flanking the SHOX coding sequence and involving its regulatory regions. An additional duplication of 1.6–2.5 Mb on 15q25.2 that included 13 genes was also identified. The girl was adopted and the parent’s DNA was not available to establish the origin of the chromosome imbalances. Conclusions The complex phenotype observed in our patient is probably the result of the co-occurrence of rearrangements on chromosomes Xp22.1 and 15q25.2. The duplicated region on 15q25.2 region is likely to contain dosage-sensitive genes responsible for some of the clinical features observed in this patient, whereas the extreme short stature and the skeletal anomalies are likely attributable to the comorbidity of GHD and copy number variants in the SHOX region.http://link.springer.com/article/10.1186/s12920-018-0445-8Short statureSHOXEnhancersCGH array |
| spellingShingle | Alice Monzani Deepak Babu Simona Mellone Giulia Genoni Antonella Fanelli Flavia Prodam Simonetta Bellone Mara Giordano Co-occurrence of genomic imbalances on Xp22.1 in the SHOX region and 15q25.2 in a girl with short stature, precocious puberty, urogenital malformations and bone anomalies BMC Medical Genomics Short stature SHOX Enhancers CGH array |
| title | Co-occurrence of genomic imbalances on Xp22.1 in the SHOX region and 15q25.2 in a girl with short stature, precocious puberty, urogenital malformations and bone anomalies |
| title_full | Co-occurrence of genomic imbalances on Xp22.1 in the SHOX region and 15q25.2 in a girl with short stature, precocious puberty, urogenital malformations and bone anomalies |
| title_fullStr | Co-occurrence of genomic imbalances on Xp22.1 in the SHOX region and 15q25.2 in a girl with short stature, precocious puberty, urogenital malformations and bone anomalies |
| title_full_unstemmed | Co-occurrence of genomic imbalances on Xp22.1 in the SHOX region and 15q25.2 in a girl with short stature, precocious puberty, urogenital malformations and bone anomalies |
| title_short | Co-occurrence of genomic imbalances on Xp22.1 in the SHOX region and 15q25.2 in a girl with short stature, precocious puberty, urogenital malformations and bone anomalies |
| title_sort | co occurrence of genomic imbalances on xp22 1 in the shox region and 15q25 2 in a girl with short stature precocious puberty urogenital malformations and bone anomalies |
| topic | Short stature SHOX Enhancers CGH array |
| url | http://link.springer.com/article/10.1186/s12920-018-0445-8 |
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