Heterozygous variants in ZBTB7A cause a neurodevelopmental disorder associated with symptomatic overgrowth of pharyngeal lymphoid tissue, macrocephaly, and elevated fetal hemoglobin.
Charlotte von der Lippe, Kristian Tveten, Trine E Prescott, Øystein L Holla, Øyvind L Busk, Katherine B Burke, Francis H Sansbury, Júlia Baptista, Andrew E Fry, Derek Lim, Stephen Jolles, Jennifer Evans, Deborah Osio, Carol Macmillan, Irene Bruno, Flavio Faletra, Salvador Climent, Roser Urreitzi, Janet Hoenicka, Francesc Palau, Ana S A Cohen, Kendra Engleman, Dihong Zhou, Shivarajan M Amudhavalli, Médéric Jeanne, Frédérique Bonnet-Brilhault, Jonathan Lévy, Séverine Drunat, Nicolas Derive, Marte G Haug, Wenche M Thorstensen
American journal of medical genetics. Part A 2022 JanBy clinical whole exome sequencing, we identified 12 individuals with ages 3 to 37 years, including three individuals from the same family, with a consistent phenotype of intellectual disability (ID), macrocephaly, and overgrowth of adenoid tissue. All 12 individuals harbored a rare heterozygous variant in ZBTB7A which encodes the transcription factor Zinc finger and BTB-domain containing protein 7A, known to play a role in lympho- and hematopoiesis. ID was generally mild. Fetal hemoglobin (HbF) fraction was elevated 2.2%-11.2% (reference value <2% in individuals > 6 months) in four of the five individuals for whom results were available. Ten of twelve individuals had undergone surgery at least once for lymphoid hypertrophy limited to the pharynx. In the most severely affected individual (individual 1), airway obstruction resulted in 17 surgical procedures before the age of 13 years. Sleep apnea was present in 8 of 10 individuals. In the nine unrelated individuals, ZBTB7A variants were novel and de novo. The six frameshift/nonsense and four missense variants were spread throughout the gene. This is the first report of a cohort of individuals with this novel syndromic neurodevelopmental disorder. © 2021 Wiley Periodicals LLC.
Citation
Charlotte von der Lippe, Kristian Tveten, Trine E Prescott, Øystein L Holla, Øyvind L Busk, Katherine B Burke, Francis H Sansbury, Júlia Baptista, Andrew E Fry, Derek Lim, Stephen Jolles, Jennifer Evans, Deborah Osio, Carol Macmillan, Irene Bruno, Flavio Faletra, Salvador Climent, Roser Urreitzi, Janet Hoenicka, Francesc Palau, Ana S A Cohen, Kendra Engleman, Dihong Zhou, Shivarajan M Amudhavalli, Médéric Jeanne, Frédérique Bonnet-Brilhault, Jonathan Lévy, Séverine Drunat, Nicolas Derive, Marte G Haug, Wenche M Thorstensen. Heterozygous variants in ZBTB7A cause a neurodevelopmental disorder associated with symptomatic overgrowth of pharyngeal lymphoid tissue, macrocephaly, and elevated fetal hemoglobin. American journal of medical genetics. Part A. 2022 Jan;188(1):272-282
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PMID: 34515416
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