Variants in KMT2A in Three Individuals with Previous Suspicion of 22q11.2 Deletion Syndrome

Autor(es)

Silveira, Henrique Garcia ; Steiner, Carlos Eduardo ; Toccoli, Giovana ; Angeloni, Luise Longo ; Heleno, Julia Londero ; Spineli-Silva, Samira ; dos Santos, Ana Mondadori ; Vieira, Tarsis Paiva ; Melaragno, Maria Isabel ; Gil-da-Silva-Lopes, Vera Lucia

• Tipo de documento: Artigo Científico
• Fonte: GENES; v. 15, n. 2, p. 10-pg., 2024-02-01.

Resumo

The condition known as 22q11.2 deletion syndrome (MIM #188400) is a rare disease with a highly variable clinical presentation including more than 180 features; specific guidelines for screening individuals have been used to support clinical suspicion before confirmatory tests by Brazil's Craniofacial Project. Of the 2568 patients listed in the Brazilian Database on Craniofacial Anomalies, 43 individuals negative for the 22q11.2 deletion syndrome were further investigated through whole-exome sequencing. Three patients (6.7%) presented with heterozygous pathogenic variants in the KMT2A gene, including a novel variant (c.6158+1del) and two that had been previously reported (c.173dup and c.3241C>T); reverse phenotyping concluded that all three patients presented features of Wiedemann-Steiner syndrome, such as neurodevelopmental disorders and dysmorphic facial features (n = 3), hyperactivity and anxiety (n = 2), thick eyebrows and lower-limb hypertrichosis (n = 2), congenital heart disease (n = 1), short stature (n = 1), and velopharyngeal insufficiency (n = 2). Overlapping features between 22q11.2 deletion syndrome and Wiedemann-Steiner syndrome comprised neuropsychiatric disorders and dysmorphic characteristics involving the eyes and nose region; velopharyngeal insufficiency was seen in two patients and is an unreported finding in WDSTS. Therefore, we suggest that both conditions should be included in each other's differential diagnoses. (AU)

• Processo FAPESP: 18/08890-9 - Detecção e consequências de desequilíbrios no genoma humano
• Beneficiário: Társis Antônio Paiva Vieira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/21644-0 - Impacto de variantes genéticas na estabilidade do genoma e seus efeitos no fenótipo
• Beneficiário: Maria Isabel de Souza Aranha Melaragno
• Modalidade de apoio: Auxílio à Pesquisa - Temático