Heterozygous variants in ZBTB7A cause a neurodevelopmental disorder associated with symptomatic overgrowth of pharyngeal lymphoid tissue, macrocephaly, and elevated fetal hemoglobin
Por:
von der Lippe, C, Tveten, K, Prescott, T, Holla, O, Busk, O, Burke, K, Sansbury, F, Baptista, J, Fry, A, Lim, D, Jolles, S, Evans, J, Osio, D, Macmillan, C, Bruno, I, Faltera, F, Climent, S, Urreitzi, R, Hoenicka, J, Palau, F, Cohen, A, Engleman, K, Zhou, D, Amudhavalli, S, Jeanne, M, Bonnet-Brilhault, F, Levy, J, Drunat, S, Derive, N, Haug, M and Thorstensen, W
Ahead of Print:
1 sep 2021
Resumen:
By 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 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.
Filiaciones:
von der Lippe, C:
Telemark Hosp Trust, Dept Med Genet, Skien, Norway
Tveten, K:
Telemark Hosp Trust, Dept Med Genet, Skien, Norway
Prescott, T:
Telemark Hosp Trust, Dept Med Genet, Skien, Norway
Holla, O:
Telemark Hosp Trust, Dept Med Genet, Skien, Norway
Busk, O:
Telemark Hosp Trust, Dept Med Genet, Skien, Norway
Burke, K:
Cardiff & Vale Univ Hlth Board, Univ Hosp Wales, All Wales Med Genom Serv, Cardiff, Wales
Sansbury, F:
Cardiff & Vale Univ Hlth Board, Univ Hosp Wales, All Wales Med Genom Serv, Cardiff, Wales
Baptista, J:
Royal Devon & Exeter NHS Fdn Trust, Exeter Genom Lab, Exeter, Devon, England
Univ Exeter, Inst Biomed & Clin Sci, Med Sch, Exeter, Devon, England
Fry, A:
Cardiff & Vale Univ Hlth Board, Univ Hosp Wales, All Wales Med Genom Serv, Cardiff, Wales
Cardiff Univ, Sch Med, Div Canc & Genet, Cardiff, Wales
Lim, D:
Birmingham Womens & Childrens NHS Fdn Trust, West Midlands Reg Genet Serv, Clin Genet, Birmingham, W Midlands, England
Jolles, S:
Univ Hosp Wales, Immunodeficiency Ctr Wales, Cardiff, Wales
Evans, J:
Univ Hosp Wales, Dept Paediat, Cardiff, Wales
Osio, D:
Birmingham Womens & Childrens NHS Fdn Trust, West Midlands Reg Genet Serv, Clin Genet, Birmingham, W Midlands, England
Macmillan, C:
Univ Chicago, Dept Pediat, Chicago, IL 60637 USA
Bruno, I:
IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy
Faltera, F:
IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy
:
Hosp Gen Ontinyent, Pediat Serv, Ontinyent, Spain
Urreitzi, R:
Inst Recerca St Joan Deu, Dept Clin Biochem, Barcelona, Spain
Inst Recerca St Joan Deu, CIBERER, Barcelona, Spain
Hoenicka, J:
Inst Recerca St Joan Deu, CIBERER, Barcelona, Spain
Inst Recerca St Joan Deu, Lab Neurogenet & Mol Med, IPER, Barcelona, Spain
Palau, F:
Inst Recerca St Joan Deu, CIBERER, Barcelona, Spain
Inst Recerca St Joan Deu, Lab Neurogenet & Mol Med, IPER, Barcelona, Spain
Inst Recerca St Joan Deu, Dept Genet Med IPER, Barcelona, Spain
Univ Barcelona, Sch Med & Hlth Sci, Hosp Clin, Barcelona, Spain
Univ Barcelona, Sch Med & Hlth Sci, Div Pediat, Barcelona, Spain
Cohen, A:
Childrens Mercy Hosp, Dept Pathol & Lab Med, Kansas City, MO USA
Childrens Mercy Hosp, Genom Med Ctr, Kansas City, MO USA
Univ Missouri, Kansas City Sch Med, Kansas City, MO USA
Engleman, K:
Univ Missouri, Kansas City Sch Med, Kansas City, MO USA
Childrens Mercy Hosp, Div Clin Genet, Kansas City, MO USA
Zhou, D:
Univ Missouri, Kansas City Sch Med, Kansas City, MO USA
Childrens Mercy Hosp, Div Clin Genet, Kansas City, MO USA
Amudhavalli, S:
Univ Missouri, Kansas City Sch Med, Kansas City, MO USA
Childrens Mercy Hosp, Div Clin Genet, Kansas City, MO USA
Jeanne, M:
Ctr Hosp Reg Univ, Serv Genet, Tours, France
Univ Tours, INSERM, iBrain, UMR1253, Tours, France
Ctr Hosp Reg Univ, Excellence Ctr Autism & Neurodev Disorders, Tours, France
Bonnet-Brilhault, F:
Univ Tours, INSERM, iBrain, UMR1253, Tours, France
Ctr Hosp Reg Univ, Excellence Ctr Autism & Neurodev Disorders, Tours, France
Levy, J:
Robert Debre Univ Hosp, APHP, Dept Genet, Paris, France
Lab Biol Med Multisites SeqOIA, Paris, France
Drunat, S:
Robert Debre Univ Hosp, APHP, Dept Genet, Paris, France
Lab Biol Med Multisites SeqOIA, Paris, France
Derive, N:
Lab Biol Med Multisites SeqOIA, Paris, France
Haug, M:
St Olays Univ Hosp, Dept Med Genet, Trondheim, Norway
Thorstensen, W:
St Olays Univ Hosp, Dept Otolaryngol Head & Neck Surg, Trondheim, Norway
Norwegian Univ Sci & Technol NTNU, Dept Neuromed & Movement Sci, Trondheim, Norway
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