Diapositiva 1

1
THE RING 14 SYNDROME CLINICAL AND MOLECULAR
DEFINITION OF A RARE CONDITION Giovanni Neri,
MD1, Laura Seminara, PhD1, Daniela Orteschi,
PhD1, Giuseppe Gobbi, MD2, Simona Giovannini,
MD2, Elvio Della Giustina, MD3, Angela Scarano,
MD3, Marcella Zollino, MD1 1Istituto di Genetica
Medica, Università Cattolica del Sacro Cuore,
Roma 2Neuropsichiatria Infantile, Ospedale
Maggiore, Bologna 3Neuropsichiatria Infantile,
Arcispedale S. Maria Nuova, Reggio Emilia, Italy
Materials and methods
Introduction

• Genetic Tests
• 1. RBG-banded chromosomes (100 cells)
• 2. Locus-specific FISH with probes (total 62)
  spanning the entire chromosome 14q
• 3. Array-CGH
• - BAC array-CGH, 1Mb 8 patients
• oligonucleotide array-CGH (Agilent) 4x44B, 75Kb
  4 patients
• 4. Microsatellite segregation analysis

• Subjects 30
• 20 ring 14
• 11 males/9 females
• Aged 3-36 years
• 9 linear deletions
• 4 males/5 females
• Aged 1-33 years
• 1 t(1014)(q25.3q12) balanced translocation

Ring 14 Syndrome is a rare genetic condition,
with clinical signs including -
Psychomotor delay - Seizures
- Hypotonia - Microcephaly
- Retinitis pigmentosa -
Characteristic face
Results
Ring 14 perinatal period
Ring 14 facial characteristics
Ring 14 Physical anomalies
Major malformations absent
Minor skeletal anomalies (scoliosis)
Café-au-lait spots Retinal
anomalies Acquired microcephaly
Pregnancy - uneventful IUGR
uncommon Delivery - at term -
normal caesarean section
uncommon Birth - normal weight
low BW in large 14q deletions -
normal length - head circumference
normal, microcephaly possible
High forehead Linear
eyebrows Hypolastic sopraorbital
ridges Deep set eyes
Short palpebral fissures/
hypotelorism High nasal bridge
Long/asymmetric face Full
cheeks Small downturned mouth
corners Ear anomalies
Ring 14 Neuropsychology and behavior
Hypotonia Seizures Mental retardation Good
natured behavior, with hyperactivity and
occasional aggressiveness
Ring 14 relevant clinical signs
Ring 14 Genetics
FISH
Distance from 14 q tel
Deletion size (Mb)
- Ring complete 6/20
30 - Ring with deletions 14/20
70 - Mosaicism with monosomy 14
CGH Ring with deletion duplication
1/12 8 UPD (14)
Absent Parental origin Maternal
30 Paternal 70
73 M18 /

• RP11-73M18

(3 Mb)

• EPILEPSY
• Mental retardation
• Susceptibility to infections
• RETINAL ANOMALIES
• Behavior disorders

• RP11-435F10

(1.5 Mb)
2,5
p11.2q32.3

• RP11-815P21

(1.2 Mb)
Present

• 14qter (telomere)

Deleted
Extent and mapping of different deletions
Phenotypic map
Ring 14 Linear 14q
deletions
Proximal Distal Seizures
MR Visual impairment
Susceptibilty to infections Behavior
disorders Scoliosis
Acquired microcephaly

Genes
Visual impairment Epilepsy Microcephaly MR
(/-) Brain abnormalities
NRL RPGRIP1 FOXG1
14q11.2q12
Infections susceptibility MR () Behavior
disorders Scoliosis
IGH
14q32
ACKNOWLEDGEMENTS We gratefully acknowledge the
financial support of the Associazione Ring
14 We also thank the patients with the families
for participating in this study