Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Report of the First Clinical Case of a Moroccan Kabuki Patient with a Novel MLL2 Mutation.

ABSTRACT: Kabuki syndrome (also known as Niikawa-Kuroki syndrome) is a rare autosomal disorder, characterized by an unusual face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, mental retardation, and immunological defects. Point mutations and large intragenic deletions and duplications of the mixed lineage leukemia 2 (MLL2) and exons deletions of lysine demethylase 6A (-KDM6A) genes have been identified as its underlying causes. We report on the first description of a Moroccan Kabuki syndrome patient with typical facial features, developmental delay, finger pads, and other anomalies carrying a novel splice site mutation in the MLL2 gene that produces a truncated and likely pathogenetic form of MLL2 protein.

SUBMITTER: Ratbi I

PROVIDER: S-EPMC3638999 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Report of the First Clinical Case of a Moroccan Kabuki Patient with a Novel MLL2 Mutation.

Ratbi I I Fejjal N N Micale L L Augello B B Fusco C C Lyahyai J J Merla G G Sefiani A A

Molecular syndromology 20130130 3

Kabuki syndrome (also known as Niikawa-Kuroki syndrome) is a rare autosomal disorder, characterized by an unusual face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, mental retardation, and immunological defects. Point mutations and large intragenic deletions and duplications of the mixed lineage leukemia 2 (MLL2) and exons deletions of lysine demethylase 6A (-KDM6A) genes have been identified as its underlying causes. We report on the first description o ...[more]

PMID: 23653588

Similar Datasets

A novel MLL2 gene mutation in a Korean patient with Kabuki syndrome.

Project description:Kabuki syndrome (KS) is a rare genetic disease with a distinctive dysmorphic face, intellectual disability, and multiple congenital abnormalities. KS is inherited in an autosomal dominant manner. As the primary cause of KS, MLL2 mutations have been identified in 56-76% of affected individuals who have been tested, suggesting that there may be additional genes associated with KS. Recently, a few KS individuals have been found to have de novo partial or complete deletions of an X chromosome gene, KDM6A, which encodes a histone demethylase that interacts with MLL2. Nevertheless, mutations in MLL2 are the major cause of KS. Although there are a few reports of KS patients in Korea, none of these had been confirmed by genetic analysis. Here, we report a case of a Korean patient with clinical features of KS. Using direct sequencing, we identified a frameshift heterozygous mutation for MLL2: (c.5256_5257delGA;p.Lys1753Alafs*34). Clinically, the patient presented with typical facial features, and diagnosis of KS was based on the diagnostic criteria. While KS is a rare disease, other malformations that overlap with those found in individuals with KS are common. Hence, the diagnosis of KS by mutational analysis can be a valuable method for patients with KS-like syndromes. Furthermore, in the near future, other genes could be identified in patients with KS without a detectable MLL2 mutation.

| S-EPMC3764261 | biostudies-literature

Infrequent Manifestations of Kabuki Syndrome in a Patient with Novel MLL2 Mutation.

Project description:We present a case of a 9-month-old Hispanic female with Kabuki syndrome with some infrequent manifestations including a single umbilical artery, butterfly vertebrae, a small larynx, a preauricular pit, microtia with internal ear abnormalities, abnormal calcium metabolism, premature thelarche, neonatal/persistent hypoglycemia and eventration of the diaphragm. She was found to have a previously unreported nonsense MLL2 mutation. This is the first case that includes all such findings occurring simultaneously that was genotyped.

| S-EPMC3507269 | biostudies-literature

A novel frameshift mutation in the XPC gene in a Moroccan patient: a case report.

Project description:BackgroundXeroderma pigmentosum is an autosomal recessive inherited disease. The diagnosis is essentially based on clinical findings and the family history. This genodermatosis is genetically heterogeneous; to date, nine genes have been associated to this disorder. Based on the result of many studies, xeroderma pigmentosum complementation group C is the most common form of xeroderma pigmentosum. A founder mutation in the XPC gene was reported in the Maghreb region of northern Africa. According to these findings, the Department of Medical Genetics in Rabat offers molecular diagnosis by screening for the recurrent mutation c.1643_1644delTG which represents 74% of all the probands with xeroderma pigmentosum.Case presentationWe describe the case of a 21-year-old Moroccan son of consanguineous parents diagnosed with xeroderma pigmentosum on the basis of sun-exposed skin abnormalities and bilateral ocular involvement. A molecular study led to the identification of a new frameshift insertion of four nucleotides in exon 9.ConclusionsTo the best of our knowledge, this mutation has not been described. The sequencing of the ninth exon should be proposed as first line molecular analysis for all Moroccan patients with xeroderma pigmentosum.

| S-EPMC5471900 | biostudies-literature

Clinical and molecular report of novel GALC mutations in Moroccan patient with Krabbe disease: case report.

Project description:BackgroundKrabbe disease (KD) or globoid cell leukodystrophy is an autosomal recessive lysosomal disorder, which affects metabolic and neurologic systems. This pathology has different forms. Infantile onset is about 85% to 90% of individuals with Krabbe disease. Disorder's onset is characterized, in early childhood, by hyperirritability, psychomotor deterioration associated to episodes of fever. To date, all reported cases have been attributed to mutations in galactosylceramidase gene (GALC gene) that encodes an enzyme which degrades galactosyl-sphingolipids (galactosylceramide, psychosine), essential in myelin production. A child compounded with two new mutations in the GALC gene was detected.Case presentationAn eleven month old male child of Moroccan origin presented to our genetic consultation with severe symptoms that included hypotonia, fever, vision loss and feeding difficulties. He was suffering from the 4th month of life. Krabbe disease was suspected. Galactocerebrosidase deficiency was confirmed by biochemical analysis. DNA sequencing revealed a novel heterozygous compound mutation in GALC gene. The child was compounded with two mutations c.860G > A; p.Cys287Tyr and c.1622G > A; p.Trp541*.ConclusionThese new mutations could affect GALC structure and therefore its function. The identification of these mutations and their associated phenotypes are important to predict the prognosis and to confer to families an adequate genetic counseling.

| S-EPMC4644339 | biostudies-literature

A novel KMT2D mutation resulting in Kabuki syndrome: A case report.

Project description:Kabuki syndrome (KS) is a rare genetic syndrome characterized by multiple congenital anomalies and varying degrees of mental retardation. Patients with KS often present with facial, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies and immunological defects. Mutation of the lysine methyltransferase 2D (KMT2D) gene (formerly known as MLL2) is the primary cause of KS. The present study reported the case of a 4‑year‑old Chinese girl who presented with atypical KS, including atypical facial features, unclear speech and suspected mental retardation. A diagnosis of KS was confirmed by genetic testing, which revealed a nonsense mutation in exon 16 of KMT2D (c.4485C>A, Tyr1495Ter). To the best of our knowledge, this is a novel mutation that has not been reported previously. The present case underscores the importance of genetic testing in KS diagnosis.

| S-EPMC5042757 | biostudies-literature

A novel mutation in the ABCD1 gene of a Moroccan patient with X-linked adrenoleukodystrophy: case report.

Project description:BackgroundX-linked adrenoleukodystrophy (X-ALD; OMIM: 300100) is the most common peroxisomal disease caused by mutations in the ATP-binding cassette, sub-family D member 1 gene or ABCD1 (geneID: 215), the coding gene for the adrenoleukodystrophy protein (ALDP), which is an ATP-binding transport protein associated to an active transport of very long chain fatty acids (VLCFAs). Dysfunction of ALDP induces an accumulation of VLCFAs in all tissues leading to a neurodegenerative disorder that involves the nervous system white matter.Case presentationIn our case report, magnetic resonance imaging (MRI) as well as the high levels of VLCFAs prompted the diagnosis the X-ALD. Molecular analysis of ABCD1 gene have shown a pathogenic homozygous nonsense mutation (c.1677C > G; p.(Tyr559*)) in exon 7.ConclusionThus, we identified here a novel mutation in the ABCD1 gene in a Moroccan patient causing X-linked adrenoleukodystrophy.

| S-EPMC4660798 | biostudies-literature

Mutation spectrum of MLL2 in a cohort of Kabuki syndrome patients.

Project description:BackgroundKabuki syndrome (Niikawa-Kuroki syndrome) is a rare, multiple congenital anomalies/mental retardation syndrome characterized by a peculiar face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, and immunological defects. Recently mutations in the histone methyl transferase MLL2 gene have been identified as its underlying cause.MethodsGenomic DNAs were extracted from 62 index patients clinically diagnosed as affected by Kabuki syndrome. Sanger sequencing was performed to analyze the whole coding region of the MLL2 gene including intron-exon junctions. The putative causal and possible functional effect of each nucleotide variant identified was estimated by in silico prediction tools.ResultsWe identified 45 patients with MLL2 nucleotide variants. 38 out of the 42 variants were never described before. Consistently with previous reports, the majority are nonsense or frameshift mutations predicted to generate a truncated polypeptide. We also identified 3 indel, 7 missense and 3 splice site.ConclusionsThis study emphasizes the relevance of mutational screening of the MLL2 gene among patients diagnosed with Kabuki syndrome. The identification of a large spectrum of MLL2 mutations possibly offers the opportunity to improve the actual knowledge on the clinical basis of this multiple congenital anomalies/mental retardation syndrome, design functional studies to understand the molecular mechanisms underlying this disease, establish genotype-phenotype correlations and improve clinical management.

| S-EPMC3141365 | biostudies-literature

Novel KDM6A splice-site mutation in kabuki syndrome with congenital hydrocephalus: a case report.

Project description:BackgroundKabuki syndrome (KS) is a rare congenital anomaly syndrome affecting multiple organs. Two genes have been shown to be mutated in patients with KS: lysine (K)-specific demethylase 6A (KDM6A) and lysine (K)-specific methyltransferase 2D (KMT2D, formerly MLL2). Although the congenital clinical characteristic is helpful in diagnosis of the KS, there are no reports of specific findings in fetuses that might suggest the syndrome prenatally.Case presentationIn this study, we described a male patient with a novel KDM6A splicing in exon(exon4) and flanking intron(intron3)-exon boundaries characterized by congenital hydrocephalus which had never been reported before. The male patient had inherited the c.335-1G > T splice site mutation from his mother who had fewer dysmorphic features than the patient who displayed a more severe phenotype with multiple organ involvement. Our research suggests that congenital hydrocephalus may accompany KS type 2, which improve the knowledge on KS further more.ConclusionsBased on genetic and clinical features, suggest that the c.335-1G > T splicing mutation in KDM6A causing KS-2 disease. At least for this case, we suggest that congenital hydrocephalus is closely associated with KS type 2.

| S-EPMC6276138 | biostudies-literature

Analysis of MLL2 gene in the first Brazilian family with Kabuki syndrome.

Project description:Most patients with Kabuki syndrome (KS) are the only person in their family with the condition. However, familial cases of KS have been described showing evidence that this syndrome can be inherited as a dominant trait with variable expressivity. We report on two related individuals with facial findings characteristic of KS. The proposita had arched eyebrows, long and upward slanting palpebral fissures, cleft lip and palate, retromicrognathia, brachydactyly of hands and feet, stubby fingers, nail hypoplasia, and prominent finger pads. Her mother had eyebrows with dispersed lateral half, long and upward slanting palpebral fissures, retrognathia, abnormal and posteriorly rotated ears, prominent finger pads, brachydactyly of feet, learning difficulties, and psychomotor development delay. DNA sequencing revealed a novel missense mutation in the MLL2 gene in both the proposita and her mother. The mutation (p.R5432Q) was found in the exon 51, within the SET domain of the gene, which confers methyltransferase activity on the protein. Therefore, the epigenetic and transcriptional regulatory properties of this protein may be altered and this suggests that the mutation is the cause of phenotype observed in both the patient and her mother. The clinical signs and the molecular evidence in this family further support the notion that KS is an autosomal dominant condition with variable expressivity. To our knowledge this is the first report of a Brazilian family with recurrence of this syndrome.

| S-EPMC3724514 | biostudies-literature

Neonatal hyperinsulinemic hypoglycemia: case report of kabuki syndrome due to a novel KMT2D splicing-site mutation.

Project description:BackgroundPersistent neonatal hypoglycemia, owing to the possibility of severe neurodevelopmental consequences, is a leading cause of neonatal care admission. Hyperinsulinemic hypoglycemia is often resistant to dextrose infusion and needs rapid diagnosis and treatment. Several congenital conditions, from single gene defects to genetic syndromes should be considered in the diagnostic approach. Kabuki syndrome type 1 (MIM# 147920) and Kabuki syndrome type 2 (MIM# 300867), can be associated with neonatal hyperinsulinemic hypoglycemia.Patient presentationWe report a female Italian (Sicilian) child, born preterm at 35 weeks gestation, with persistent hypoglycemia. Peculiar facial dysmorphisms, neonatal hypotonia, and cerebellar vermis hypoplasia raised suspicion of Kabuki syndrome. Hyperinsulinemic hypoglycemia was confirmed with glucagon test and whole-exome sequencing (WES) found a novel heterozygous splicing-site mutation (c.674-1G > A) in KMT2D gene. Hyperinsulinemic hypoglycemia was successfully treated with diazoxide. At 3 months corrected age for prematurity, a mild global neurodevelopmental delay, postnatal weight and occipitofrontal circumference growth failure were reported.ConclusionsKabuki syndrome should be considered when facing neonatal persistent hypoglycemia. Diazoxide may help to improve hyperinsulinemic hypoglycemia. A multidisciplinary and individualized follow-up should be carried out for early diagnosis and treatment of severe pathological associated conditions.

| S-EPMC7499940 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data