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Start Over Descriptor "brachydactyly-mental retardation syndrome" Topic growth disorders
2 results on '"brachydactyly-mental retardation syndrome"'

1. HDAC8 Loss of Function and SHOX Haploinsufficiency: Two Independent Genetic Defects Responsible for a Complex Phenotype.

Author

Severi G, Bonora E, Perri A, Scarano E, Mazzanti L, Isidori F, Zuntini R, Menabò S, and Graziano C

Subjects
Child, Comparative Genomic Hybridization, De Lange Syndrome genetics, Female, Growth Disorders genetics, Haploinsufficiency, Humans, Osteochondrodysplasias genetics, Pedigree, Phenotype, Exome Sequencing, De Lange Syndrome diagnosis, Frameshift Mutation, Gene Deletion, Growth Disorders diagnosis, Histone Deacetylases genetics, Osteochondrodysplasias diagnosis, Repressor Proteins genetics, Short Stature Homeobox Protein genetics
Abstract

We report a patient with developmental delay, brachydactyly type E, short stature, and tetralogy of Fallot. Brachydactyly-mental retardation syndrome (BDMR) was suspected based on the phenotype; however, array CGH excluded a 2q37 deletion, but identified a deletion encompassing the SHOX gene. BDMR is characterized by cognitive impairment, skeletal abnormalities involving hands and feet, short stature, and overweight. Most affected individuals carry relatively large 2q37 deletions encompassing HDAC4. This gene encodes a histone deacetylase involved in epigenetic regulation of cell growth and differentiation, specifically during endochondral bone formation in chondrocyte hypertrophy. Since SHOX haploinsufficiency can cause skeletal defects and short stature but would not fully explain the clinical picture of this patient, exome sequencing was performed, and a heterozygous HDAC8 frameshift mutation was identified. HDAC8 is a distinct histone deacetylase involved in cohesin recycling and is responsible for an X-linked dominant Cornelia de Lange-like phenotype. A new blended clinical phenotype may be explained by the result of a dual molecular diagnosis, which represents a combination of 2 independent genetic defects, with relevant implications for genetic counseling, clinical management, and prognosis., (© 2019 S. Karger AG, Basel.)

Published
2019
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2. HDAC8 Loss of Function and SHOX Haploinsufficiency: Two Independent Genetic Defects Responsible for a Complex Phenotype

Author

Severi G., Bonora E., Perri A., Scarano E., Mazzanti L., Isidori F., Zuntini R., Menabo S., Graziano C., Severi G., Bonora E., Perri A., Scarano E., Mazzanti L., Isidori F., Zuntini R., Menabo S., and Graziano C.

Subjects
Haploinsufficiency, Osteochondrodysplasias, Whole Exome Sequencing, Histone Deacetylases, Brachydactyly-mental retardation syndrome, Short Stature Homeobox Protein, Growth Disorder, Histone Deacetylase, De Lange Syndrome, Exome Sequencing, Humans, Osteochondrodysplasia, Child, Frameshift Mutation, Growth Disorders, Comparative Genomic Hybridization, Repressor Protein, Dual molecular diagnosi, Pedigree, Repressor Proteins, Phenotype, HDAC8, Female, Gene Deletion, SHOX, Human
Abstract

We report a patient with developmental delay, brachydactyly type E, short stature, and tetralogy of Fallot. Brachydactyly-mental retardation syndrome (BDMR) was suspected based on the phenotype; however, array CGH excluded a 2q37 deletion, but identified a deletion encompassing the SHOX gene. BDMR is characterized by cognitive impairment, skeletal abnormalities involving hands and feet, short stature, and overweight. Most affected individuals carry relatively large 2q37 deletions encompassing HDAC4. This gene encodes a histone deacetylase involved in epigenetic regulation of cell growth and differentiation, specifically during endochondral bone formation in chondrocyte hypertrophy. Since SHOX haploinsufficiency can cause skeletal defects and short stature but would not fully explain the clinical picture of this patient, exome sequencing was performed, and a heterozygous HDAC8 frameshift mutation was identified. HDAC8 is a distinct histone deacetylase involved in cohesin recycling and is responsible for an X-linked dominant Cornelia de Lange-like phenotype. A new blended clinical phenotype may be explained by the result of a dual molecular diagnosis, which represents a combination of 2 independent genetic defects, with relevant implications for genetic counseling, clinical management, and prognosis.

Published
2018

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