POSTER PRESENTATION Open Access

Prenatal diagnosis of autosomal recessiveosteopetrosis: a case reportMehul Mistri1, Harsh Patel1, Tanmay Tanna2*, Chitra Ankleshwaria1, Frenny Sheth1, Jayesh Sheth1

From International Conference on Human Genetics and 39th Annual Meeting of the Indian Society ofHuman Genetics (ISHG)Ahmadabad, India. 23-25 January 2013

BackgroundAutosomal Recessive Osteopetrosis (ARO) or MalignantInfantile Osteopetrosis (MIOP) is a congenital disordercharacterized by increased bone density on radiographs.It is known to be caused by mutations that cause loss offunction in the TCIRG1, CLCN7 or OSTM1 genes. Classicsymptoms include bone marrow failure, visual and hearingimpairment, pancytopenia and extramedullary hematopoi-esis leading to hepatosplenomegaly. The disease is lethalin infancy and the only curative treatment known isHematopoietic Stem Cell Transplantation (HSCT). Prena-tal diagnosis is done either by autoradiography or byidentifying disease causing mutation.

Case presentationWe present a family with consanguineous marriage witha male child born at full term with an uneventful incidentand normal Apgar score. The child had normal mile-stones of development till two years of age. After this, hedeveloped symptoms such as low platelet, low hemo-globin, splenomegaly and hydrocephalus. The patient wasstarted with fortnightly blood transfusions. Clinically hewas suspected to have osteopetrosis and investigated formutations in TCIRG1 gene. Targeted exon sequencingidentified the patient to be homozygous for a novel non-sense pathological mutation p.R426X (c.1276 C>T) inTCIRGI gene. He expired in the course of treatment atthe age of 2.5 years. Subsequently, both parents werefound to be heterozygous carriers for the same mutation.

Prenatal counseling was advised for any future pregnan-cies. In the subsequent pregnancy, prenatal testing wasdone at 11 weeks of gestation using uncultured chorionicvillus sample (CVS) to investigate for the aforementionedmutation. Analysis of genomic DNA obtained fromuncultured CV has shown heterozygous status forTCIRGI p.R426X (c.1276 C>T) mutation. The family wasinformed of the carrier status of the fetus and theirpsychological trauma and stress was alleviated.

ConclusionsPrenatal Diagnosis of Malignant Infantile Osteopetrosis(MIOP) through targeted sequencing of genomic DNAobtained from uncultured CV can be carried out oncethe mutation has been identified in an index case. Thisnovel mutation also provides a new insight into themolecular basis of the disease which can be utilized formolecular diagnosis.

Authors’ details1Institute of Human Genetics, FRIGE House, Ahmedabad-15, Gujarat, India.2National Institute of Technology Warangal, Andhra Pradesh 506004, India.

Published: 21 January 2014

doi:10.1186/1755-8166-7-S1-P125Cite this article as: Mistri et al.: Prenatal diagnosis of autosomalrecessive osteopetrosis: a case report. Molecular Cytogenetics 20147(Suppl 1):P125.

2National Institute of Technology Warangal, Andhra Pradesh 506004, IndiaFull list of author information is available at the end of the article

Mistri et al. Molecular Cytogenetics 2014, 7(Suppl 1):P125http://www.molecularcytogenetics.org/content/7/S1/P125

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