Dataset Information

Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

ABSTRACT: Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage-sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF, including four individuals with inherited changes in BPTF. In addition to the previously described features, individuals in this cohort exhibited mild brain abnormalities, seizures, scoliosis, and a variety of ophthalmologic complications. These results further support the broad and multi-faceted complications due to haploinsufficiency of BPTF.

SUBMITTER: Glinton KE

PROVIDER: S-EPMC8048530 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

Glinton Kevin E KE Hurst Anna C E ACE Bowling Kevin M KM Cristian Ingrid I Haynes Devon D Adstamongkonkul Dusit D Schnappauf Oskar O Beck David B DB Brewer Carole C Parikh Aditi Shah AS Shinde Deepali N DN Donaldson Alan A Brautbar Ariel A Koene Saskia S van Haeringen Arie A Piton Amélie A Capri Yline Y Furlan Margherita M Gardella Elena E Møller Rikke Steensbjerre RS van de Beek Irma I Zuurbier Linda L Lakeman Phillis P Bayat Allan A Bayat Allan A Martinez Julian J Signer Rebecca R Torring Pernille M PM Engelund Morten Buch MB Gripp Karen W KW Amlie-Wolf Louise L Henderson Lindsay B LB Midro Alina T AT Tarasów Eugeniusz E Stasiewicz-Jarocka Beata B Moskal-Jasinska Diana D Vos Paul P Boschann Felix F Stoltenburg Corinna C Puk Oliver O Mero Inger-Lise IL Lossius Kristine K Mignot Cyril C Keren Boris B Acosta Guio Johanna C JC Briceño Ignacio I Gomez Alberto A Yang Yaping Y Stankiewicz Pawel P

American journal of medical genetics. Part A 20210131 5

Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage-sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, w ...[more]

PMID: 33522091

Similar Datasets

Project description:Background: Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies (NEDDFSA) is a rare syndromic disorder characterized by global neurodevelopmental delay, early-onset hypotonia, poor overall growth, poor speech/language ability, and additional common phenotypes such as eye anomalies, joint hypermobility, and skeletal anomalies of the hands and feet. NEDDFSA is caused by heterozygous pathogenic variants in the ZMIZ1 gene on chromosome 10q22.3 with autosomal dominant (AD) mode of inheritance. All the 32 reported cases with variants in ZMIZ1 gene had a genetic background in Caucasian, Hispanic, North African, and Southeastern Asian. Until now, there are no reports of Chinese patients with ZMIZ1 pathogenic variants. Methods: A 5-year-old girl was found to have the characteristic phenotypes of NEDDFSA. Array-Comparative Genomic Hybridization (array-CGH) and whole exome sequencing (WES) were applied for the trio of this female patient. Sanger sequencing was used to verify the selected variants. A comprehensive molecular analysis was carried out by protein structure prediction, evolutionary conservation, motif scanning, tissue-specific expression, and protein interaction network to elucidate pathogenicity of the identified ZMIZ1 variants. Results: The karyotype was 46, XX with no micro-chromosomal abnormalities identified by array-CGH. There were 20 variants detected in the female patient by WES. A de novo heterozygous missense variant (c.2330G > A, p.Gly777Glu, G777E) was identified in the exon 20 of ZMIZ1. No variants of ZMIZ1 were identified in the non-consanguineous parents and her healthy elder sister. It was predicted that G777E was pathogenic and detrimental to the spatial conformation of the MIZ/SP-RING zinc finger domain of ZMIZ1. Conclusion: Thus far, only four scientific articles reported deleterious variants in ZMIZ1 and most of the cases were from Western countries. This is the first report about a Chinese patient with ZMIZ1 variant. It will broaden the current knowledge of ZMIZ1 variants and variable clinical presentations for clinicians and genetic counselors.

Dataset Information

Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

Publications

Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets