56 Abbreviations HI, hearing impairment; ICMR, Indian Council of Medical Research; NSHL, nonsyndromic hearing loss; CIs, cochlear implants; ARNSHL, autosomal recessive nonsydromic hearing loss; MLPA, multiplex ligation-dependent probe amplifcation; RBCs, red blood cells; WBCs, white blood cells; EDTA, ethylenediaminetetraacetic acid; TE, tris(hydroxymethyl)animoethane- ethylenediaminetetraacetic acid; Tris, tris(hydroxymethyl)animoethane; dNTPs, deoxynucleotides; ABI, Applied Biosystems Inc.; F, female; M, male Departments of 1 ENT, Head and Neck Surgery, 2 Human Genetics, and 3 Speech Language and Hearing Sciences, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India *To whom correspondence should be addressed. arunachalamravikumar1954@gmail.com © American Society for Clinical Pathology 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com Mutation Analysis Using Multiplex Ligation-Dependent Probe Amplifcation in Consanguineous Families in South India with a Child with Profound Hearing Impairment Ravi Kumar Arunachalam, MS, 1* Teena Koshy, PhD, 2 Vettriselvi Venkatesan, PhD, 2 Gladys Prathiba Dawson, MASLP, 3 Solomon Franklin Durairaj Paul, PhD, 2 Pratibha George, MS 1 Laboratory Medicine 2020;51:56-65 DOI: 10.1093/labmed/lmz027 ABSTRACT Background: Consanguineous marriage, a common practice in South India, increase the incidence of autosomal recessive diseases such as nonsyndromic hearing loss (NSHL) in offspring. This trend was noted in the children with hearing impairment (HI) who received cochlear implants (CI) at our University hospital in Porur, Chennai, India. To ascertain the genetic etiology of HI in these patients, we performed multiplex ligation-dependent probe amplifcation (MLPA) analysis. Methods: A total of 25 families who had a child with NSHL were included in the study. MLPA screening of GJB2, GJB6, and GJB3 was performed for all the recruited individuals. Results: The pathogenic p.W24X* mutation of GJB2 was detected in 2 patients; both of their parents were heterozygous carriers. Both families had a second-degree consanguineous marriage. Conclusion: This study has important implications for molecular-diagnosis strategy and genetic counseling for families with HI in South India. Keywords: consanguinity, cochlear implant, South India, MLPA ARNSHL, GJB2 gene The most common sensory defcit in humans is hearing impairment (HI). The Indian Council of Medical Research (ICMR) has reported the prevalence of HI in the urban areas of India as being 6.8%. 1 It is estimated that 30,000 infants are born with congenital sensorineural HI in India each year 2 ; the results of epidemiology studies 3 have revealed that in Southern India, the incidence is 6 times the world- wide average. Approximately 50% of the reported congenital cases are hereditary and classifed as nonsyndromic hearing loss (NSHL), due to the absence of associated clinical symp- toms. 2 Congenital NSHL is generally a result of environmental causes, such as medications, or genetic mutations. The de- velopment, differentiation, and maintenance of the inner ear require a large number of genes; mutations in those genes will lead to sensorineural hearing loss. So far, nearly 85 genes that cause NSHL have been located, with specifc prevalence in diverse ethnic groups and geographic regions (Figure 1). 3,4 Consanguinity is considered to play a major role in her- editary NSHL because autosomal recessive inheritance accounts for 75% to 80% of the cases. In the remaining 20% to 25% of the cases, the inheritance of NSHL is auto- somal dominant inheritance, with X-linked and mitochon- drial modes of inheritance reported in less than 1% of the cases. 3,4 Downloaded from https://academic.oup.com/labmed/article/51/1/56/5509817 by guest on 16 June 2022