Abstract
From 1995 to 2017 an abnormally high number of tibia hemimelia (TH) patients from
the Maku subregion in the West Azarbaijan province of Iran were referred to our orthopedic
department for treatment. Regarding the occurrence of TH in many families in a restricted
region and negative results of available genetic tests, we hypothesized that a founder
mutation etiology that is different from previous known genetic disorders might produce
the trait of TH in our patients. Through a retrospective study, we collected demographic
data including date of birth, patients and parents place of birth, sex, type of TH,
presence of other musculoskeletal anomalies, and treatment from the patients who were
referred to our department. We obtained a blood sample for genetic studies. We carried
out genetic studies in cytogenetics and molecular levels on a patient with familial
TH. The prevalence of TH in the Maku subregion of West Azarbaijan was 149.5 (95% confidence
interval [CI]: 68.4–283.8) per 1 million live birth. The patients did not fit with
any known syndromes with TH. Genetic evaluations of a patient with familial history
of TH in this case series exhibited no detectable change in both cytogenetic and molecular
levels. There was an obvious increased prevalence rate of TH in this province and
particularly in the Maku subregion. The cytogenetic locations for known syndromic
TH are not responsible for the observed anomalies in our patients. Our next step for
detecting possible genetic mutations in our patients would be mutation analysis via
very high-resolution whole genomic sequencing in more patients or genetic linkage
study.
Keywords
congenital anomaly - genetic mutation - tibia hemimelia
