Kaufman oculocerebrofacial syndrome in sisters with novel compound heterozygous mutation in <i>UBE3B</i>

Pedurupillay, Christeen Ramane J.; Barøy, Tuva; Holmgren, Asbjørn; Blomhoff, Anne; Vigeland, Magnus Dehli; Sheng, Ying; Frengen, Eirik; Strømme, Petter; Misceo, Doriana

doi:10.1002/ajmg.a.36944

Cited by 16 publications

(22 citation statements)

References 26 publications

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“…KOS is a rare type of the BMRS, caused by biallelic mutations of the ubiquitin protein ligase E3B gene (Basel‐Vanagaite et al, ; Flex et al, ). Beyond the short and narrow palpebral fissures and intellectual disability, affected individuals typically show hypotonia, microcephaly, sparse and thin hair, sparse and laterally broad eyebrows, malformed ears and/or external meati, and feeding difficulties (Basel‐Vanagaite et al, , ; Flex et al, ; Kariminejad et al, ; Pedurupillay et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Kaufman oculocerebrofacial syndrome (KOS), a rare autosomal recessive type of the BMRS, was first described in 1971, but it was not until 2012 that its genetic cause was discovered via the identification of biallelic mutations in the ubiquitin ligase E3B encoding gene UBE3B (Basel‐Vanagaite et al, ; Flex et al, ; Kaufman et al, ) With only 15 published patients with biallelic UBE3B mutations reported so far, knowledge on the phenotypic and molecular characteristics of KOS is still expanding. (Basel‐Vanagaite et al, , ; Flex et al, ; Kariminejad et al, ; Pedurupillay et al, ) Apart from the original four patients of Kaufman, five patients with the clinical diagnosis of KOS have been reported between 1971 and 2013 (Briscioli, Manoukian, Selicorni, Livini, & Lalatta, ; Figuera, Garcia‐Cruz, Ramirez‐Duenas, Rivera‐Robles, & Cantu, ; Jurenka & Evans, ; Murano, ). The patient of Briscioli et al () had no blepharophimosis and was later subject of UBE3B sequencing by Flex et al () but no disease‐causing mutation was identified.…”

Section: Introductionmentioning

confidence: 99%

“…Other frequent findings include anteverted nares, micro‐retrognathia, ectodermal anomalies (skin tags, sparse, and thin hair), respiratory distress, genital anomalies, reduced serum cholesterol values, and unspecific structural brain anomalies, especially agenesis or hypoplasia of the corpus callosum. (Flex et al, ; Kariminejad et al, ) Structural cardiac defects are not common findings in KOS, only four patients were reported to date (Basel‐Vanagaite et al, ; Pedurupillay et al, ). In one individual, hypoplastic and absent terminal phalanges of fingers were described (Kariminejad et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Kaufman oculocerebrofacial syndrome: Novel UBE3B mutations and clinical features in four unrelated patients

Yilmaz

Szakszon

Altmann

et al. 2017

American J of Med Genetics Pt A

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The "blepharophimosis-mental retardation" syndromes (BMRS) consist of a group of clinically and genetically heterogeneous congenital malformation syndromes, where short palpebral fissures and intellectual disability associate with a distinct set of other morphological features. Kaufman oculocerebrofacial syndrome represents a rare and recently reevaluated entity within the BMR syndromes and is caused by biallelic mutations of UBE3B. Affected individuals typically show microcephaly, impaired somatic growth, gastrointestinal and genitourinary problems, ectodermal anomalies and a characteristic face with short, upslanted palpebral fissures, depressed nasal bridge. and anteverted nares. Here we present four patients with five novel UBE3B mutations and propose the inclusion of clinical features to the characteristics of Kaufman oculocerebrofacial syndrome, including prominence of the cheeks and limb anomalies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Kaufman oculocerebrofacial syndrome: Novel UBE3B mutations and clinical features in four unrelated patients

Yilmaz

Szakszon

Altmann

et al. 2017

American J of Med Genetics Pt A

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“…3, 5 It is also worth noting that a subset of the UBE3B variants that occur upstream of the HECT domain are either missense, truncating or frameshift and hence, are perceived to compromise the enzymatic activity of the HECT domain or the function of UBE3B protein. Even though UBE3B is expressed in the brain and craniofacial structures during embryonic development, 2 it is unclear how mutations in UBE3B lead to KOS.…”

Section: Discussionmentioning

confidence: 99%

“…1–5 There is marked variability in the phenotype. The variability in the phenotype has caused some patients to be initially diagnosed as having other entities such as Toriello-Carey syndrome or a “new syndrome”.…”

Section: Introductionmentioning

confidence: 99%

Kaufman oculo-cerebro-facial syndrome in a child with small and absent terminal phalanges and absent nails

et al. 2016

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Background Kaufman oculo-cerebro-facial syndrome (KOS) is caused by recessive UBE3B mutations and presents with microcephaly, ocular abnormalities, distinctive facial morphology, low cholesterol levels and intellectual disability. We describe a child with microcephaly, brachycephaly, hearing loss, ptosis, blepharophimosis, hypertelorism, cleft palate, multiple renal cysts, absent nails, small or absent terminal phalanges, absent speech and intellectual disability. Syndromes which were initially considered include DOORS syndrome, Coffin-Siris syndrome and Dubowitz syndrome. Methods Clinical investigations coupled with, karyotype analysis, array-CGH, exome and Sanger sequencing were performed to characterize the condition in this child. Results Sanger sequencing was negative for the DOORS syndrome gene TBC1D24 but exome sequencing identified a homozygous deletion in UBE3B (NM_183415:c.3139_3141del, p.1047_1047del) located within the terminal portion of the HECT domain. This finding coupled with the presence of characteristic features such as brachycephaly, ptosis, blepharophimosis, hypertelorism, short palpebral fissures, cleft palate and developmental delay, allowed us to make a diagnosis of KOS. Conclusion Our findings highlight the importance of considering KOS as a differential diagnosis for patients under evaluation for DOORS syndrome and expand the phenotype of KOS to include small or absent terminal phalanges, nails, and the presence of hallux varus and multicystic dysplastic kidneys.

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Blepharophimosis‐ptosis‐intellectual disability syndrome: A report of nine Egyptian patients with further expansion of phenotypic and mutational spectrum

Zaki

Otaify

Ismail

et al. 2020

American J of Med Genetics Pt A

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Blepharophimosis-ptosis-intellectual disability syndrome (BPID) is an extremely rare recognizable blepharophimosis intellectual disability syndrome (BID). It is caused by biallelic variants in the UBE3B gene with only 24 patients described worldwide. Herein, we report on the clinical, brain imaging and molecular findings of additional nine patients from six unrelated Egyptian families. Patients presented with the characteristic features of the syndrome including blepharophimosis, ptosis, upslanted palpebral fissures with epicanthic folds, hypertelorism, long philtrum, high arched palate, micrognathia, microcephaly, and intellectual disability. Other findings were congenital heart disease (5 patients), talipes equinovarus (5 patients), genital anomalies (5 patients), autistic features (4 patients), cleft palate (2 patients), hearing loss (2 patients), and renal anomalies (1 patient). New or rarely reported findings were spherophakia, subvalvular aortic stenosis and hypoplastic nails, and terminal phalanges. Brain MRI, performed for 7 patients, showed hypogenesis or almost complete agenesis of corpus callosum. Genetic studies revealed five novel homozygous UBE3B variants. Of them, the c.1076G>A (p.W359*) was found in three patients from two unrelated families who shared similar haplotype suggesting a likely founder effect. Our results strengthen the clinical, dysmorphic, and brain imaging characteristic of this unique type of BID and extend the mutational spectrum associated with the disorder. K E Y W O R D S blepharophimosis-intellectual disability syndromes, blepharophimosis-ptosis-intellectual disability syndrome, Egyptian patients, novel variants, UBE3B gene 1 | INTRODUCTION Blepharophimosis-intellectual disability syndromes (BID) represent a clinically and genetically heterogeneous group of disorders characterized by intellectual disability, short palpebral fissures along with distinct morphological findings (Yilmaz et al., 2018). So far, more than 100 BID syndromes have been described in the literature and the phenotypic overlap in many of them pointed to a marked difficulty in differential diagnosis and nosology (Dentici, Mingarelli, & Dallapiccola, 2011). They include Dubowitz syndrome (MIM 223370),

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Kaufman oculocerebrofacial syndrome in sisters with novel compound heterozygous mutation in UBE3B

Cited by 16 publications

References 26 publications

Kaufman oculocerebrofacial syndrome: Novel UBE3B mutations and clinical features in four unrelated patients

Kaufman oculocerebrofacial syndrome: Novel UBE3B mutations and clinical features in four unrelated patients

Kaufman oculo-cerebro-facial syndrome in a child with small and absent terminal phalanges and absent nails

Blepharophimosis‐ptosis‐intellectual disability syndrome: A report of nine Egyptian patients with further expansion of phenotypic and mutational spectrum

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