A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.
Growth deficiency, psychomotor delay, and facial dysmorphism was originally described in a male patient in 1989 by Wiedemann et al. and later in 2000 by Steiner et al. Wiedemann-Steiner syndrome (WSS) has since been described only a few times in the literature, with the phenotypic spectrum both expanding and becoming more delineated with each patient reported. We report on the clinical and molecular features of monozygotic twins with a de novo mutation in KMT2A. Single nucleotide polymorphism (SNP) microarray was done on both twins and whole-exome sequencing was done using both parents and one of the affected twins. SNP microarray confirmed that they were monozygotic twins. A de novo heterozygous variant (p. Arg1083*) in the KMT2A gene was identified through whole-exome sequencing, confirming the diagnosis of WSS. In this study, we have identified a de novo mutation in KMT2A associated with psychomotor developmental delay, facial dysmorphism, short stature, hypertrichosis cubiti, and small kidneys. This finding in monozygotic twins gives specificity to the WSS. The description of more cases of WSS is needed for further delineation of this condition. Small kidneys with normal function have not been described in this condition in the medical literature before.
University of Newcastle, Callaghan, New South Wales, Australia.
Sophie
S
Dunkerton
Department of Immunology, John Curtin School of Medical Research, Australian National University, Canberra City, Australian Capital Territory, Australia.
Matthew
M
Field
Department of Immunology, John Curtin School of Medical Research, Australian National University, Canberra City, Australian Capital Territory, Australia.
Vicki
V
Cho
Australian Phenomics Facility, The Australian National University, Canberra City, Australian Capital Territory, Australia.
Edward
E
Bertram
Australian Phenomics Facility, The Australian National University, Canberra City, Australian Capital Territory, Australia.
Belinda
B
Whittle
Hunter Genetics, Waratah, New South Wales, Australia.
Alexandra
A
Groves
University of Newcastle, Callaghan, New South Wales, Australia.|Hunter Genetics, Waratah, New South Wales, Australia.
Himanshu
H
Goel
D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D003286:Contracture / Q000235:genetics*; D004200:Diseases in Twins / Q000235:genetics*; D059472:Exome / Q000235:genetics; D019066:Facies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006130:Growth Disorders / Q000235:genetics*; D006579:Heterozygote; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008831:Microcephaly / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013577:Syndrome; D014430:Twins, Monozygotic / Q000235:genetics*
C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase
KMT2A; MLL; SNP; Wiedemann-Steiner syndrome; de novo; hypertrichosis cubiti; monozygotic twins