Aïcha Boughalem ^1* Viorica CIORNA MONFERRATO ² Natacha SLOBODA ² Amelie Guegan ¹ Francois Page ¹ Sophie Zimmer ¹ Marion Benazra ¹ Pascale Kleinfinger ¹ Laurence Lohmann ¹ Mylene Valduga ¹ Aline Receveur ¹ Fernando Martin ³ Detlef Trost ^3*

• ¹ Department of Human Genetics, Laboratoire CERBA SA, Saint Ouen L'aumône, France
• ² Génétique Médicale et Oncogénétique, Centre Hospitalier Régional Metz, Thionville, Metz, Lorraine, France
• ³ Laboratoire CERBA SA, Saint Ouen L'aumône, France

We are reporting an index patient with complete insensitivity to pain and a history of painless fractures, joint hypermobility, and behavioural problems. The index patient descends from a family with notable cases among his maternal relatives, including his aunt, a mother's first cousin, both of whom suffer from congenital insensitivity to pain. The patient had normal results for prior genetic testing: fragile-X, chromosomal micro-array, and exome sequencing. Optical genome mapping detected a homozygous deletion affecting the noncoding 5' area and the first non-coding exon of the SCN9A gene in all affected family members, compatible with recessive disease transmission. Pathogenic homozygous loss of function variants in the SCN9A gene are associated with impaired pain sensation in humans.Optical genome mapping can thus detect pathogenic structural variants in patients without molecular etiology by standard diagnostic procedures and seems to be a more accessible diagnostic tool than short read or long read whole genome sequencing. Keywords Optical genome mapping (OGM), SCN9A, insensitivity to pain, non-coding structural variants, structural variant (SV) detection.