Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD.

Sylvie Picker-Minh,Fowzan S Alkuraya,Mais Hashem,Angela M Kaindl,Nadine Kraemer,Eissa Faqeih,Cyril Mignot,Béatrice Dubern,Patrice Josset,Diane Doummar

doi:10.1186/s13023-016-0433-z

Abstract

Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) has been recently linked to biallelic mutation of the peptidyl-tRNA hydrolase 2 gene PTRH2. Two index patients with IMNEPD in the original report had multiple neurological symptoms such as postnatal microcephaly, intellectual disability, developmental delay, sensorineural deafness, cerebellar atrophy, ataxia, and peripheral neuropathy. In addition, distal muscle weakness and abnormalities of thyroid, pancreas, and liver were found. Here, we report five further IMNEPD patients with a different homozygous PTRH2 mutation, broaden the phenotypic spectrum of the disease and differentiate common symptoms and interindividual variability in IMNEPD associated with a unique mutation. We thereby hope to better define IMNEPD and promote recognition and diagnosis of this novel disease entity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0433-z) contains supplementary material, which is available to authorized users.

Highlights

The infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD; MIM#616263) was recently reported by us as a novel disease entity in two individuals from a consanguineous family of Yazidian-Turkish descent [1]
We recently highlighted the role of peptidyl-tRNA hydrolase 2 gene (PTRH2) for human development by linking a homozygous PTRH2 gene nonsense mutation (c.269_270delCT, p.A90fs) to the disease infantile multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) [1]
Progressive cerebellar atrophy and ataxia imposed as key features of IMNEPD in the index family with a homozygous nonsense mutation of PTRH2

Summary

Introduction

The infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD; MIM#616263) was recently reported by us as a novel disease entity in two individuals from a consanguineous family of Yazidian-Turkish descent [1]. We further demonstrated the association of a homozygous nonsense mutation in the PTRH2 gene (MIM*608625) to IMNEPD through functional and molecular data in human and mouse [1]. The two index patients in the original report presented with postnatal microcephaly, moderate intellectual disability, abnormal rhythmic rapid activity on EEG, sensorineural deafness, and delayed speech development. They suffered from distal muscle weakness and delayed motor milestones, and later developed progressive ataxia and progressive cerebellar atrophy. Peripheral demyelinating sensorimotor neuropathy and endocrine abnormalities with affection of the

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Conclusion