Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

A newly recognized 13q12.3 microdeletion syndrome characterized by intellectual disability, microcephaly, and eczema/atopic dermatitis encompassing the HMGB1 and KATNAL1 genes

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Safety of switching to Migalastat from enzyme replacement therapy in Fabry disease: Experience from the Phase 3 ATTRACT study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. First reported adult patient with TARP syndrome: A case report

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Ocular albinism with infertility and late-onset sensorineural hearing loss

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Stakeholders in psychiatry and their attitudes toward receiving pertinent and incident findings in genomic research

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. De novo mutations in MSL3 cause an X-linked syndrome marked by impaired histone H4 lysine 16 acetylation

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Risks and Recommendations in Prenatally Detected De Novo Balanced Chromosomal Rearrangements from Assessment of Long-Term Outcomes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Contingent first-trimester screening for aneuploidies with cell-free DNA in a Danish clinical setting

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Proximal deletions of the long arm of chromosome 13 have been reported only rarely. Here we present three unrelated patients with heterozygous, apparently de novo deletions encompassing 13q12.3. The patients present with moderate demonstrated or apparent intellectual disability, postnatal microcephaly, and eczema/atopic dermatitis as the predominant symptoms. In addition, they had pronounced feeding difficulties in early infancy. They displayed similar facial features such as malar flattening, a prominent nose with underdeveloped alae nasi, a smooth philtrum, and a thin vermillion of the upper lip. The proximal and distal breakpoints were clustered and the deletions spanned from 1.4 to 1.7 Mb, comprising at least 11 RefSeq genes. However, heterozygous deletions partially overlapping those observed in the present patients have been described in healthy parents of patients with Peters-Plus syndrome, an autosomal recessive disorder caused by inactivation of the B3GALTL gene. We therefore propose that the critical region of the 13q12.3 microdeletion syndrome contains only three genes, namely, KATNAL1, HMGB1, and LINC00426, a non-protein coding RNA. The KATNAL1 protein belongs to a family of microtubule severing enzymes that have been implicated in CNS plasticity in experimental models, but little is known about its function in humans. The HMGB1 protein is an evolutionarily conserved chromatin-associated protein involved in many biologically important processes. In summary, we propose that microdeletion 13q12.3 represents a novel clinically recognizable condition and that the microtubule severing gene KATNAL1 and the chromatin-associated gene HMGB1 are candidate genes for intellectual disability inherited in an autosomal dominant pattern.

Original languageEnglish
JournalAmerican Journal of Medical Genetics. Part A
Volume164A
Issue number5
Pages (from-to)1277-83
Number of pages7
ISSN1552-4825
DOIs
Publication statusPublished - May 2014

ID: 45085264