A novel mutation in <i>RNU4ATAC</i> in a patient with microcephalic osteodysplastic primordial dwarfism type I

Kılıç, Esra; Yigit, Goekhan; Ütine, Gülen Eda; Wollnik, Bernd; Mıhçı, Ercan; Nur, Banu; Boduroğlu, Koray

doi:10.1002/ajmg.a.36955

Cited by 15 publications

(19 citation statements)

References 13 publications

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“…Dry rough skin and sometimes ichthyosis are commonly observed in MOPDI but are not seen in all individuals. It is usually confined to the abdomen but may show extension to the limbs and has no relation with hydration [Nagy et al, ; Abdel‐Salam et al, , Kilic et al, ]. Our patient had dry skin since early neonatal period that has stationary course through adulthood.…”

Section: To the Editormentioning

confidence: 72%

Long‐term survival in microcephalic osteodysplastic primordial dwarfism type I: Evaluation of an 18‐year‐old male with g.55G>A homozygous mutation in RNU4ATAC

Abdel-Salam

Emam

Khalil

et al. 2015

American J of Med Genetics Pt A

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Microcephalic Osteodysplastic Primordial Dwarfism type I (MOPDI) is an autosomal recessive disorder with poorly understood biology. It is characterized by profound prenatal and postnatal somatic growth failure, developmental brain malformations and by early death in infancy [Taybi and Linder, 1967;Majewski et al., 1982]. The longest survival among the previously reported cases was 12.75-year old boy [Nagy et al., 2012] who had compound heterozygous g.30G>A and g.111G>A mutations in RNU4ATAC. Another German girl with a homozygous g.55G>A mutation was described at the age of 9-year-old [Nagy et al., 2012]. Information in the medical literature regarding long survival of MOPDI patients is limited and the clinical phenotype with age has not yet been clearly characterized, making the diagnosis amongst older patients more challenging. We report on an 18-year-old male with late presentation of MOPDI caused by g.55G>A homozygous mutation in RNU4ATAC. He had a history of motor deterioration after an episode of encephalitis in addition to severe growth retardation.The patient was the 2nd child born to healthy consanguineous parents (first cousins) when the mother was 20 and the father was 31 years old. The other sib was normal. There is a family history of maternal uncle affected with neuropsychiatric disorder. The pregnancy was uneventful and he was delivered at 30 weeks of gestation with a birth weight 1,500 g and length 35.5 cm (both 3rd centile). He was admitted to neonatal intensive care unit for 12 days because of prematurity and growth retardation. Infancy was characterized by poor weight gain and delayed motor development. During infancy and early childhood, he had multiple episodes of infections, including recurrent otitis media. In addition to this history, the father provided us with a photographic picture of our proband when he was 1-year-old with a facial appearance of sparse hair, prominent eyes and nose and small mouth (Fig. 1).His motor milestones were delayed (head support at 12 months, sitting at 3 years, stood with support at 5 years and walked independently at 7 years). He was noted to have an unsteady gait that is accompanied by frequent falls. This was long-standing and progressive and followed by spasticity and contractures of the MS. 2016. Long-term survival in microcephalic osteodysplastic primordial dwarfism type I: Evaluation of an 18-year-old male with g.55G>A homozygous mutation in RNU4ATAC.Am J Med Genet Part A 170A:277-282.

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Section: To the Editormentioning

confidence: 72%

Long‐term survival in microcephalic osteodysplastic primordial dwarfism type I: Evaluation of an 18‐year‐old male with g.55G>A homozygous mutation in RNU4ATAC

Abdel-Salam

Emam

Khalil

et al. 2015

American J of Med Genetics Pt A

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“…P1, patient 1; P2, patient 2; P3, patient 3; P4, patient 4; MED, multiple epiphyseal dysplasia; SED, spondyloepiphyseal dysplasia; SEMD, spondyloepimetaphyseal dysplasia; DD, developmental delay; ID, intellectual disability; IUGR, intrauterine growth restriction; NE, not evaluated. + reported; − not reported; ~ MOPD1 causal, reduced severity; * He et al (2011); ** Kilic et al (2015); ^ Merico et al (2015). …”

Section: Figurementioning

confidence: 99%

The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome

Farach

Little

Duker

et al. 2017

American J of Med Genetics Pt A

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RNU4ATAC pathogenic variants to date have been associated with microcephalic osteodysplastic primordial dwarfism, type 1 and Roifman syndrome. Both conditions are clinically distinct skeletal dysplasias with microcephalic osteodysplastic primordial dwarfism, type 1 having a more severe phenotype than Roifman syndrome. Some of the overlapping features of the two conditions include developmental delay, microcephaly, and immune deficiency. The features also overlap with Lowry Wood syndrome, another rare but well-defined skeletal dysplasia for which the genetic etiology has not been identified. Characteristic features include multiple epiphyseal dysplasia and microcephaly. Here, we describe three patients with Lowry Wood syndrome with biallelic RNU4ATAC pathogenic variants. This report expands the phenotypic spectrum for biallelic RNU4ATAC disorder causing variants and is the first to establish the genetic cause for Lowry Wood syndrome.

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“…Finally, severe and recurrent infections are constant in Roifman syndrome, due to impaired production of specific antibody in response to antigens stimulation, whereas serum level of IgG, IgA and IgM are generally normal or moderately low. In TALS, recurrent infections have been reported in only three cases (8,11,14), one of them having an IgG level reported as low (14). These statements suggest a continuous spectrum between these two disorders but require the description of additional patients with RNU4ATAC mutations.…”

Section: Discussionmentioning

confidence: 96%

“…A genotype–phenotype correlation is emerging concerning survival in TALS. While poor survival is associated with homozygosity for the g.51G>A mutation, patients with long‐term survival harbour other mutations, mostly g.55G>A , g.46G>A and g.30G>A in association with g.111G>A . No clear genotype–phenotype correlation can be made yet regarding other features observed in TALS.…”

Section: Discussionmentioning

confidence: 97%

Refining the phenotypical and mutational spectrum of Taybi‐Linder syndrome

Putoux

Alqahtani

Pinson³

et al. 2016

Clinical Genetics

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Taybi-Linder syndrome (TALS, OMIM 210710) is a rare autosomal recessive disorder belonging to the group of microcephalic osteodysplastic primordial dwarfisms (MOPD). This syndrome is characterized by short stature, skeletal anomalies, severe microcephaly with brain malformations and facial dysmorphism, and is caused by mutations in RNU4ATAC. RNU4ATAC is transcribed into a non-coding small nuclear RNA which is a critical component of the minor spliceosome. We report here four foetuses and four unrelated patients with RNU4ATAC mutations. We provide antenatal descriptions of this rare syndrome including unusual features found in two twin foetuses with compound heterozygosity for two rare mutations who presented with mild intrauterine growth retardation and atypical dysmorphic facial features. We also carried out a literature review of the patients described up to now with RNU4ATAC mutations, affected either with TALS or Roifman syndrome, a recently described allelic disorder.

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A novel mutation in RNU4ATAC in a patient with microcephalic osteodysplastic primordial dwarfism type I

Cited by 15 publications

References 13 publications

Long‐term survival in microcephalic osteodysplastic primordial dwarfism type I: Evaluation of an 18‐year‐old male with g.55G>A homozygous mutation in RNU4ATAC

Long‐term survival in microcephalic osteodysplastic primordial dwarfism type I: Evaluation of an 18‐year‐old male with g.55G>A homozygous mutation in RNU4ATAC

The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome

Refining the phenotypical and mutational spectrum of Taybi‐Linder syndrome

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