Format

Send to

Choose Destination
Eur J Med Genet. 2018 Jun;61(6):322-328. doi: 10.1016/j.ejmg.2018.01.009. Epub 2018 Feb 3.

First prenatal case of proximal 19p13.12 microdeletion syndrome: New insights and new delineation of the syndrome.

Author information

1
APHP, Service d'Histologie, Embryologie et Cytogénétique, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France; Faculté de Médecine Paris-Sud, Université Paris-Sud, 94276 Le Kremlin-Bicêtre cedex, France. Electronic address: minhtuannia82@yahoo.it.
2
APHP, Service d'Histologie, Embryologie et Cytogénétique, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France; Faculté de Médecine Paris-Sud, Université Paris-Sud, 94276 Le Kremlin-Bicêtre cedex, France.
3
APHP, Laboratoire de Génétique Moléculaire, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France.
4
APHP, Unité de Fœtopathologie, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France.
5
APHP, Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Hôpitaux Universitaires Paris-Sud, CHU Bicêtre, F-94275, France.
6
APHP, Service de Génétique médicale, Hôpital Necker-Enfant malades, Paris, France.
7
Service de Gynécologie-obstétrique, Hôpital Saint Joseph, Paris, France.
8
APHP, Service d'Histologie, Embryologie et Cytogénétique, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France.

Abstract

Proximal 19p13.12 microdeletion has been rarely reported. Only five postnatal cases with intellectual disability, facial dysmorphism, branchial arch defects and overlapping deletions involving proximal 19p13.12 have been documented. Two critical intervals were previously defined: a 700 kb for branchial arch defects and a 350 kb for hypertrichosis-synophrys-protruding front teeth. We describe the first prenatal case, a fetal death in utero at 39 weeks of gestation. Agilent 180K array-CGH analysis identified a heterozygous interstitial 745 kb deletion at 19p13.12 chromosome region, encompassing both previously reported critical intervals, including at least 6 functionally relevant genes: NOTCH3, SYDE1, AKAP8, AKAP8L, WIZ and BRD4. Quantitative PCR showed that the deletion occurred de novo with a median size of 753 kb. NOTCH3 and SYDE1 were candidate genes for placental pathology whilst AKAP8, AKAP8L, WIZ and BRD4 were highly expressed in the branchial arches. Molecular characterization and sequencing of candidate genes for placental pathology and branchial arch defects were carried out in order to correlate the genotype-phenotype relationship and unravel the underlying mechanism of proximal 19p13.12 microdeletion syndrome. This case also contributes to define the novel critical interval and expand the clinical phenotype spectrum of proximal 19p13.12 microdeletion syndrome.

KEYWORDS:

Branchial arch defects; Contiguous gene deletion syndrome; Novel critical interval; Prenatal diagnosis; Proximal 19p13.12 microdeletion

PMID:
29366875
DOI:
10.1016/j.ejmg.2018.01.009
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center