Congenital immunodeficiency in an individual with Wiedemann-Steiner syndrome due to a novel missense mutation in KMT2A.
Wiedemann-Steiner Syndrome (WSS) is an autosomal dominant disorder characterized by hypertrichosis, short stature, intellectual disability, developmental delay, and facial dysmorphism. Since the original reports by Wiedemann and co-workers, and Steiner and Marques, only a few cases have been described. Recently, the clinical variability of the disorder has more precisely been characterized by Jones and co-workers, who also identified heterozygous KMT2A mutations as the molecular defect underlying this condition. Here, we report on a boy with a complex phenotype overlapping WSS but exhibiting epilepsy, feeding difficulties, microcephaly, and congenital immunodeficiency with low levels of immunoglobulins as additional features. Whole exome sequencing allowed identifying a previously unreported de novo KMT2A missense mutation affecting the DNA binding domain of the methyltransferase. This finding expands the clinical phenotype associated with KMT2A mutations to include immunodeficiency and epilepsy as clinically relevant features for this disorder. © 2016 Wiley Periodicals, Inc.
Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Emilia
E
Stellacci
Rare Diseases and Genetic Disorders, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.
Roberta
R
Onesimo
Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Alessandro
A
Bruselles
Genetic Disorders and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù IRCSS, Rome, Italy.
Simone
S
Pizzi
Infantile Neuropsychiatric Unit, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.
Domenica
D
Battaglia
Rare Diseases and Genetic Disorders, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.
Chiara
C
Leoni
Rare Diseases and Genetic Disorders, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.
Giuseppe
G
Zampino
Genetic Disorders and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù IRCSS, Rome, Italy.
Marco
M
Tartaglia
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D019066:Facies; D056726:Genetic Association Studies; D006579:Heterozygote; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis* / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D010641:Phenotype; D013577:Syndrome
C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase
KMT2A; Weidemann-Steiner syndrome; congenital immunodeficiency; exome sequencing