Gene/phenotype/disorder under study
ZBTB7A, ZINC FINGER- AND BTB DOMAIN-CONTAINING PROTEIN 7A (OMIM* 605878); MACROCEPHALY, NEURODEVELOPMENTAL DELAY, LYMPHOID HYPERPLASIA, AND PERSISTENT FETAL HEMOGLOBIN; MNDLFH (OMIM # 619769)
Abstract
Pathogenic variants in ZBTB7A cause a very rare, syndromic neurodevelopmental disorder characterized by overgrowth of pharyngeal lymphoid tissue often with clinically significant upper airway obstruction, macrocephaly and intellectual disability. Increased HbF fraction in children may be a useful biomarker for the disorder.
The zinc finger and BTB domain-containing 7A transcription factor, located on chromosome 19p13.3, also known as Pokemon and lym-phoma/leukemia-related factor (LRF), is encoded by ZBTB7A, which is widely expressed in humans. ZBTB7A is required to block Notch signaling in bone marrow progenitor cells, allowing their development into B-cells, a master up-regulator of T-cell proliferation (Maedaet al., 2007).
We are interested in performing genome methylation profiling in affected individuals to investigate the possibility of a diagnostic episignature/biomarker, the clinical severity/variability and pathogenetic mechanism of the condition.
Supported by a grant from the Norwegian National Centre for Rare Diagnoses (#43066) and the Research Council of Norway (#358387).
Coordinating clinicians
Sofia Douzgou Houge – sofia.douzgou.houge@helse-bergen.no
Charlotte von Der Lippe – uxhelc@sthf.no
Institutions
Department of Medical Genetics; Haukeland University Hospital, Bergen, Norway
Telemark Hospital Trust, Skien, Norway
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: Yes (DNA methylation analysis)
2- Resampling of patients: Yes (if DNA concentration not optimal)
3- Linked to a translational/basic research project: No