Refinement of the 12q14 microdeletion syndrome: primordial dwarfism and developmental delay with or without osteopoikilosis.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_FE324EEF2698
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Titre
Refinement of the 12q14 microdeletion syndrome: primordial dwarfism and developmental delay with or without osteopoikilosis.
Périodique
European Journal of Human Genetics
Auteur(s)
Mari F., Hermanns P., Giovannucci-Uzielli M.L., Galluzzi F., Scott D., Lee B., Renieri A., Unger S., Zabel B., Superti-Furga A.
ISSN
1476-5438 (Electronic)
ISSN-L
1018-4813
Statut éditorial
Publié
Date de publication
2009
Volume
17
Numéro
9
Pages
1141-1147
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
In their studies on the molecular basis of osteopoikilosis, Menten et al have identified three individuals with microdeletions on chromosome 12q14.4, which removed several genes including LEMD3, the osteopoikilosis gene. In addition to osteopoikilosis, affected individuals had growth retardation and developmental delay. We now report a smaller 12q14.4 microdeletion in a boy with severe pre and postnatal growth failure, and mild developmental delay; the patient was small at birth and presented with poor feeding and failure to thrive during the first 2 years of life, similar to the phenotype of primordial dwarfism or severe Silver-Russell syndrome (SRS). The 12q14 deletion did not include LEMD3, and no signs of osteopoikilosis were observed on skeletal radiographs. Among the deleted genes, HMGA2 is of particular interest in relationship to the aberrant somatic growth in our patient, as HMGA2 variants have been linked to stature variations in the general population and loss of function of Hmga2 in the mouse results in the pygmy phenotype that combines pre and postnatal growth failure, with resistance to the adipogenic effect of overfeeding. Sequencing of the remaining HMGA2 allele in our patient showed a normal sequence, suggesting that HMGA2 haploinsufficiency may be sufficient to produce the aberrant growth phenotype. We conclude that the 12q14.4 microdeletion syndrome can occur with or without deletion of LEMD3 gene; in LEMD3-intact cases, the phenotype includes primordial short stature and failure to thrive with moderate developmental delay, but osteopoikilosis is absent. Such cases will likely be diagnosed as Silver-Russell-like or as primordial dwarfism.
Mots-clé
Abnormalities, Multiple/genetics, Abnormalities, Multiple/pathology, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Pair 12/genetics, Comparative Genomic Hybridization, Developmental Disabilities/pathology, Growth Disorders/pathology, Humans, Karyotyping, Male, Osteopoikilosis/pathology, Syndrome
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/03/2011 17:09
Dernière modification de la notice
20/08/2019 17:28
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