Journal of Neurological Sciences 158 (1998) 43–46 Molecular analysis of the SMN and NAIP genes in Saudi spinal muscular atrophy patients a ,c a, a ,b a ,d * Saad Al Rajeh , Ramanath Majumdar , Adnan Awada , Adetunji Adeyokunnu , a ,b c a Mohammed Al Jumah , Muneera Al Bunyan , Anna Snellen a Neurogenetics Laboratory, King Fahad National Guard Hospital, Medical Research Centre, P .O. Box 22490, Riyadh 11426, Saudi Arabia b Neurology Section, King Fahad National Guard Hospital, Riyadh 11426, Saudi Arabia c Neurology Division, King Saud University, Riyadh 11472, Saudi Arabia d Department of Pediatrics, King Fahad National Guard Hospital, Riyadh 11426, Saudi Arabia Received 29 July 1997; received in revised form 23 December 1997; accepted 30 December 1997 Abstract In this study we examined the deletion of the SMN and NAIP genes in 14 Saudi families (16 patients and 38 relatives of the patients, including parents and siblings) and six healthy Saudi volunteers. The homozygous deletions of exons 7 and 8 of the telomeric SMN gene and exon 5 of the NAIP gene were found in seven out of eight spinal muscular atrophy (SMA) type-I patients. In seven SMA type-II patients, exons 7 and 8 of telomeric SMN were deleted in six cases and exon 5 of NAIP was deleted in three cases. Three patients with SMA diagnosis did not show either of the above deletions. All control Saudi volunteers and all but two family members of the patients had both normal SMN and NAIP genes. Our results show that the incidence of NAIP deletion is higher in the more severe SMA cases and the dual deletions of the SMN and NAIP genes are more common in Saudi SMA type-I patients compared to patients of other ethnic groups.  1998 Elsevier Science B.V. Keywords: Spinal muscular atrophy; Gene deletion; SMN gene; NAIP gene; PCR; Saudi families 1. Introduction ease), patients learn to walk, but suffer from proximal muscle weakness with onset after the age of two. Proximal spinal muscular atrophy (SMA) is a neuro- The candidate region for SMA locus has been mapped muscular disorder which results in the loss of motor to chromosome 5q11.2-5q13.3 by linkage analysis neurons in the spinal cord and lower brainstem leading to [7,11,13]. Recent studies by several investigators have symmetrical progressive paralysis with muscle atrophy. shown that the SMA region is highly polymorphic in SMA is classified into three clinical groups based on age at character, with a complex genomic structure containing onset, achievement of developmental milestones and life- several genes and pseudogenes [6]. Two candidate genes span [12]. Type-I SMA, known as Werdnig–Hoffmann are known to be involved in SMA. The survival motor disease (the most severe form of SMA), is characterized by neuron gene (SMN) is present in two highly homologous severe generalized muscle weakness and hypotonia with copies, telomeric SMN (telSMN) and centromeric SMN onset between birth and six months. Death from respirato- (cenSMN) within the SMN region [10]. Both copies are ry failure usually occurs within the first two years. In types composed of nine exons which encode identical amino II (intermediate form) and III (Kugelberg–Welander dis- acid sequence. The two genes differ in their exons by only two base pairs, one in exon 7 and one in exon 8, that allow distinction of the telSMN gene from cenSMN by single * Corresponding author: Tel.: 1966 1 2520088; fax: 1966 1 2520040. strand conformation analysis (SSCA) and restriction site 0022-510X / 98 / $19.00  1998 Elsevier Science B.V. All rights reserved. PII: S0022-510X(98)00053-7