Postnatal diagnosis of 9q interstitial imbalances involving PTCH1, resulting from a familial intrachromosomal insertion.
Insertions are rare chromosomal rearrangements resulting from a three breaks mechanism. The risk of chromosomal imbalance in the offspring is estimated to be 15-50%. We have identified a familial history of direct, paracentric intrachromosomal 9q insertion, balanced in healthy members. For intrachromosomal insertions, unbalanced products in the offspring are always recombinants and in our case, reciprocal deletion and duplication of the inserted segment (9q22.31-9q31.1) were observed. These imbalances involved several genes, including PTCH1. PTCH1 haploinsufficiency causes Gorlin syndrome, an autosomal dominant disorder usually linked to the gene mutation but sometimes due to a 9q deletion. Clinical findings are different in 9q deletions and duplications including PTCH1, notably concerning the predisposition to benign and malignant tumors reported in the Gorlin syndrome. Furthermore, some features may be reciprocal. This history of intrachromosomal insertion highlights the importance of morphological cytogenetic analyses to provide an accurate genetic counseling.
Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Pontchaillou, Rennes, France.
Marina
M
Blanchard
Laboratoire de Génétique Moléculaire, CHU Pontchaillou, Rennes, France; CNRS UMR 6290 (IGDR), Université de Rennes 1, France.
Christèle
C
Dubourg
Service de Génétique Médicale, CHU Hôpital Sud, Rennes, France.
Laurent
L
Pasquier
CNRS UMR 6290 (IGDR), Université de Rennes 1, France; Service de Génétique Médicale, CHU Hôpital Sud, Rennes, France.
Sylvie
S
Odent
Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Pontchaillou, Rennes, France.
Josette
J
Lucas
Service de Génétique Médicale, CHU Hôpital Sud, Rennes, France; Laboratoire d'Anatomie et Cytologie Pathologiques, CHU Pontchaillou, Rennes, France.
Chloé
C
Quélin
Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Pontchaillou, Rennes, France.
Erika
E
Launay
Service de Génétique Médicale, CHU Hôpital Sud, Rennes, France.
Linda
L
Akloul
Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Pontchaillou, Rennes, France.
Catherine
C
Henry
Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Pontchaillou, Rennes, France; CNRS UMR 6290 (IGDR), Université de Rennes 1, France.
Marc-Antoine
MA
Belaud-Rotureau
Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Pontchaillou, Rennes, France; CNRS UMR 6290 (IGDR), Université de Rennes 1, France.
Frédéric
F
Dugay
Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Pontchaillou, Rennes, France.
Sylvie
S
Jaillard
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D016254:Mutagenesis, Insertional; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010375:Pedigree; D011956:Receptors, Cell Surface / Q000235:genetics*
C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface
Array-CGH; Chromosome 9; Interstitial deletion; Interstitial duplication; Intrachromosomal paracentric direct insertion