Central 22q11.2 deletion (LCR22 B-D) in a fetus with severe fetal growth restriction and a mother with severe systemic lupus erythematosus: Further evidence of CRKL haploinsufficiency in the pathogenesis of 22q11.2 deletion syndrome.
Am J Med Genet A
; 185(10): 3042-3047, 2021 10.
Article
em En
| MEDLINE
| ID: mdl-34196458
ABSTRACT
22q11.2 deletion syndrome (22q11.2 DS, MIM #188400) is the most common chromosomal microdeletion with an incidence of 1 in 4000 live births. 22q11.2 DS patients present with varying penetrance and a broad phenotypic spectrum including dysmorphic features, congenital heart defects, hypoplastic thymus and T-cell deficiency, and hypocalcemia. The typical deletion spans 3 Mb between 4 large blocks of repetitive DNA, known as low copy repeats (LCRs), on chromosome 22 (LCR22) A and D. This deletion is found in ~85% of 22q11.2 DS patients, while only 4-5% have central LCR22B-D (1.5 Mb) and LCR22C-D (0.7 Mb) deletions. We report on a prenatally diagnosed, inherited case of central LCR22B-D 22q11.2 DS, born to a 22-year-old female with multiple autoimmune disorders. These include Sjogren's-syndrome-related antigen A (SSA+) severe systemic lupus erythematosus (SLE) with cutaneous and discoid components and seronegative antiphospholipid syndrome. Amniocentesis was performed due to fetal growth restriction (FGR). FISH with TUPLE1 (HIRA) probe was normal; however, chromosomal microarray identified a ~737 kb heterozygous loss between LCR22B-D. Subsequently, the same deletion was identified in the mother, which included CRKL and 19 other genes but excluded HIRA and TBX1, the typical candidate genes for 22q11.2DS pathogenesis. This case explores how loss of CRKL may contribute to immune dysregulation, as seen in the multiple severe autoimmune phenotypes of the mother, and FGR. Our experience confirms the importance of thorough workup in individuals with reduced penetrance of 22q11.2 DS features or atypical clinical presentations.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Adaptadoras de Transdução de Sinal
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Síndrome de DiGeorge
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Retardo do Crescimento Fetal
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Lúpus Eritematoso Sistêmico
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
Limite:
Adult
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Female
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Humans
Idioma:
En
Revista:
Am J Med Genet A
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos