Mutations in the human ROBO1 gene in pituitary stalk interruption syndrome.

Related Articles

Mutations in the human ROBO1 gene in pituitary stalk interruption syndrome.

J Clin Endocrinol Metab. 2017 Apr 11;:

Authors: Bashamboo A, Bignon-Topalovic J, Moussi N, McElreavey K, Brauner R

Abstract
Context: Pituitary stalk interruption syndrome (PSIS) is characterised by a thin or absent pituitary stalk usually in association with an ectopic posterior pituitary and hypoplasia/aplasia of the anterior pituitary. Associated phenotypes include varied ocular anomalies, hypoglycemia, micropenis/cryptorchidism, growth failure or combined pituitary hormone deficiencies. Although genetic causes have been identified, they explain only around 5% of PSIS cases.
Objective: To identify genetic causes of PSIS by exome sequencing.
Design: Exon enrichment was performed using Agilent SureSelect Human All Exon V4. Paired-end sequencing was performed on the Illumina HiSeq2000 platform with an average sequencing coverage of x50.
Patients: Patients with unexplained PSIS were included in the study.
Results: In 5 cases of unexplained PSIS including two familial cases, we identified novel heterozygous frameshift, nonsense and missense mutations in the ROBO1 gene (p.Ala977Glnfs*40, two affected sibs; p.Tyr1114Ter, sporadic case and p.Cys240Ser affected child and paternal aunt) that controls embryonic axon guidance and branching in the nervous system. Interestingly, 4 of the 5 cases of PSIS also presented with ocular anomalies including hypermetropia with strabismus as well as ptosis.
Conclusions: These data suggest that mutations in ROBO1 contribute to PSIS and associated ocular anomalies.

PMID: 28402530 [PubMed - as supplied by publisher]

http://ift.tt/2p9KV3x